Immunocytochemical localization of tubulin and microtubule-associated protein 2 during the development of hippocampal neurons in culture
Open accessAbstract
n dissociated-cell cultures prepared from the embryonic rat hippocampus, neurons establish both axons and dendrites, which differ in geometry, in ultrastructure, and in synaptic polarity. We have used immunocytochemistry with monoclonal antibodies to study the regional distribution of beta-tubulin and micro-tubule-associated protein 2 (MAP2) in hippocampal cultures and their localization during early stages of axonal and dendritic development. After development for a week or more in culture, when axons and dendrites were well- differentiated, the distribution of these two proteins was quite different. Beta-tubulin was present throughout the nerve cell, in soma, dendrites, and axon. It was also present in all classes of non-neuronal cells, astrocytes, fibroblasts, and a presumptive glial progenitor cell. In contrast, MAP2 was preferentially localized to nerve cells; within neurons, MAP2 was present in soma and dendrites, but little or no immunostaining was detectable in axons. Both beta-tubulin and MAP2 were present in nerve cells at the time of plating. From the earliest stages of process extension, beta-tubulin was present in all neuronal processes, both axons and dendrites. Surprisingly, MAP2 was also initially present in both axons and dendrites, extending as far as the axonal growth cone. With subsequent development, MAP2 staining was selectively lost from the axon so that after 1 week in vitro little or no axonal staining remained. Taken together with earlier results (Caceres et al., 1984a), these data indicate that the establishment of neuronal polarity, as manifested by the molecular differentiation of the axonal and dendritic cytoskeleton, occurs largely under endogenous control, even under culture conditions in which cell interactions are greatly restricted.(ABSTRACT TRUNCATED AT 250 WORDS)
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Written from the paper’s full text.
TL;DR
In dissociated embryonic rat hippocampal cultures, beta-tubulin was present in axons, dendrites, soma, and non-neuronal cells, whereas MAP2 was preferentially localized to soma and dendrites in mature neurons. Unexpectedly, MAP2 was initially present in both axons and dendrites, including axonal growth cones, and was selectively lost from axons over the first week in culture.
Key findings
- In mature cultures (7–35 d in vitro), beta-tubulin immunoreactivity was present throughout neurons—soma, dendrites, and even the thinnest axons—and in astrocytes, fibroblasts, and presumptive glial progenitor cells; MAP2 was intensely stained in perikarya and dendrites but showed little or no axonal staining.
- At plating, both beta-tubulin and MAP2 were present in nerve cells; within 1–2 d, MAP2 immunoreactivity was present in all developing processes, including axons, and could be followed to axonal tips as far as 150 µm from cell bodies.
- By 3–4 d in culture, MAP2 staining in axons appeared preferentially in distal axonal regions, sometimes restricted to the growth cone and immediately proximal axon; by about the end of the first week, axonal MAP2 staining had largely disappeared.
- After 1 d in culture, when MAP2 was still uniformly distributed in axons and dendrites, dendrites were already elongating about 5× more slowly than axons, indicating that MAP2 presence does not determine dendritic identity.
Methods
- Hippocampal neurons were prepared from 17–20-d-old rat fetuses, dissociated after trypsin treatment, and plated onto polylysine-treated coverslips at 5,000–15,000 cells/cm²; coverslips were co-cultured facing confluent astroglial monolayers in MEM with N2 supplement and 0.1% ovalbumin.
- Immunocytochemistry used monoclonal antibodies against beta-tubulin (clones Tu9b, Tu12, Tu27) and MAP2 (clones AP9, AP13), with several fixation/permeabilization procedures including paraformaldehyde/glutaraldehyde, cold methanol, and Triton X-100 extraction; staining was visualized by peroxidase-antiperoxidase and diaminobenzidine.
- Analysis was qualitative light-microscopic immunocytochemistry, with controls omitting primary antibody or preabsorbing with purified antigen.
Limitations
- The paper states that MAP2 distribution in situ has not been studied at comparably early stages, so it is unknown whether axons transiently contain MAP2 during normal development in situ.
- The paper states that axonal MAP2 staining could be an artifact of dissociation and culture, and that the functional role of MAP2 in developing axons is not known.
- Evident from the text: the study is qualitative immunocytochemistry without quantification, and the culture system uses glial co-culture and trophic support, so it may not fully reproduce in vivo cell interactions.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
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Claims the paper makes
12 of 78 cited sources checked · 9 supported · 0 flagged · accuracy not yet measured
- Premisecitation§ Results
The non-neuronal cells in these cultures include astrocytes, fibroblasts, and presumptive glial progenitor cells similar to those described by Raff et al. (1983) in cultures of optic nerve.
“The non-neuronal cells present in these cultures, which have been identified using cell-type specific markers (A. Hodson and G. Banker, unpublished observations), include astrocytes, fibroblasts, and presumptive glial progenitor cells similar to those described by Raff et al. (1983) in cultures of optic nerve.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Raff et al. (1983) source
- Interpretationreasoning§ Organization of microtubules in hippocampal neurons in culture
The sorting and transport of materials that occur in neurons must be considerably more sophisticated than that in other polarized cells.
“Thus, the sorting and transport of materials that occur in neurons must be considerably more sophisticated than that in other polarized cells (e.g., Matlin and Simons, 1984).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Matlin and Simons, 1984 source
- Premisecitation§ Localization of MAP2 at early stages of neuronal development
Microtubules are found along the full length of dendrites, extending to the base of dendritic growth cones.
“They are found along the full length of the dendrites, extending to the base of the dendritic growth cones (Hinds and Hinds, 1972;Skoff and Hamburger, 1974;Vaughn et al., 1974).”
Quote in the paperNot a substantial claim1 of 3 sources checked - Findingown data
MAP2 is preferentially localized to nerve cells in hippocampal cultures.
“In contrast, MAP2 was preferentially localized to nerve cells; within neurons, MAP2 was present in soma and dendrites, but little or no immunostaining was detectable in axons.”
- Also stated in: § Results · hedged
“Hence, MAP2 appears to be preferentially expressed by neuronal cells in hippocampal cultures, just as it is in situ (Caceres et al., 1984b;Huber and Matus, 1984b).”
Quote in the paperSubstantial claim - Also stated in: § Results · hedged
- Findingown data
Beta-tubulin is present throughout the nerve cell, in soma, dendrites, and axon.
“Beta-tubulin was present throughout the nerve cell, in soma, dendrites, and axon.”
- Also stated in: § Results · plain
“neuron-in the perikaryon, throughout all portions of the dendrites that could be followed from the cell body, and in even the thinnest of the axons.Every process that could be seen by phase-contrast microscopy also displayed immunoreactivity for beta-tubulin.”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data
Beta-tubulin is present in all classes of non-neuronal cells in hippocampal cultures, including astrocytes, fibroblasts, and a presumptive glial progenitor cell.
“It was also present in all classes of non-neuronal cells, astrocytes, fibroblasts, and a presumptive glial progenitor cell.”
- Also stated in: § Results · plain
“All were stained with antibodies specific for tubulin, but little immunoreactive MAP2 was detected in any of these classes of non-neuronal cells.”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data
With subsequent development, MAP2 staining is selectively lost from the axon so that after 1 week in vitro little or no axonal staining remains.
“With subsequent development, MAP2 staining was selectively lost from the axon so that after 1 week in vitro little or no axonal staining remained.”
- Also stated in: § Loss of MAP2 during axonal development · plain
“By about the end of the first week in culture, axonal MAP2 staining had largely disappeared.”
Quote in the paperSubstantial claim - Also stated in: § Loss of MAP2 during axonal development · plain
- Findingown data
Both beta-tubulin and MAP2 are present in nerve cells at the time of plating.
“Both beta-tubulin and MAP2 were present in nerve cells at the time of plating.”
- Also stated in: § Distribution of tubulin and MAP2 early in neuronal development · plain
“Nearly all cells reacted with antibodies against both MAP2 and beta-tubulin (data not shown).”
Quote in the paperSubstantial claim - Also stated in: § Distribution of tubulin and MAP2 early in neuronal development · plain
- Findingown data§ Results
The restricted localization of MAP2 was observed after development in vitro for times ranging from 7 to 35 d.
“This restricted localization of MAP2 was observed after development in vitro for times ranging from 7 to 35 d.”
Quote in the paperSubstantial claim - Findingown data
MAP2 is initially present in both axons and dendrites, extending as far as the axonal growth cone.
“Surprisingly, MAP2 was also initially present in both axons and dendrites, extending as far as the axonal growth cone.”
- Also stated in: § Distribution of tubulin and MAP2 early in neuronal development · plain
“immunoreactivity for MAP2 was present in all of the developing processes, including the developing axon.”
- Also stated in: § Discussion · plain
“MAP2 staining, seen in the bright-field micrograph (C), is present along the full length of the axon as far as the base of its growth cone (gc).”
Quote in the paperSubstantial claim - Also stated in: § Distribution of tubulin and MAP2 early in neuronal development · plain
- Findingown data§ Results
Little or no MAP2 immunoreactivity is detected in non-neuronal cells in hippocampal cultures.
“All were stained with antibodies specific for tubulin, but little immunoreactive MAP2 was detected in any of these classes of non-neuronal cells.”
Quote in the paperSubstantial claim - Findingown data
From the earliest stages of process extension, beta-tubulin is present in all neuronal processes, both axons and dendrites.
“From the earliest stages of process extension, beta-tubulin was present in all neuronal processes, both axons and dendrites.”
- Also stated in: § Distribution of tubulin and MAP2 early in neuronal development · plain
“All of the processes, both axons and dendrites, were from the outset heavily stained following exposure to antibodies against beta-tubulin.”
Quote in the paperSubstantial claim - Also stated in: § Distribution of tubulin and MAP2 early in neuronal development · plain
- Findingown data§ Localization of MAP2 at early stages of neuronal development
At the outset of development, MAP2 is present in all of the neuronal processes, axons as well as dendrites.
“At the outset of development, MAP2 is present in all of the neuronal processes, axons as well as dendrites.”
Quote in the paperSubstantial claim - Findingown data§ Loss of MAP2 during axonal development
When 3 or 4 d cultures were examined after fixation with low concentrations of glutaraldehyde together with formaldehyde, MAP2 immunoreactivity appeared preferentially localized in the distal portions of the axonal arborization, as well as throughout the dendrites.
“When 3 or 4 d cultures were examined after fixation with low concentrations of glutaraldehyde together with formaldehyde, MAP2 immunoreactivity appeared to be preferentially localized in the distal portions of the axonal arborization, as well as throughout the dendrites.”
Quote in the paperSubstantial claim - Findingown data§ Discussion
In well-differentiated hippocampal neurons in culture, MAP2 is preferentially localized to cell bodies and dendrites, with little or no labeling of axons or non-neuronal cells.
“In well-differentiated hippocampal neurons in culture we observed that MAP2 was preferentially localized to the cell bodies and dendrites; little or no labeling of axons or of non-neuronal cells was seen.”
Quote in the paperSubstantial claim - Findingown data§ Localization of MAP2 at early stages of neuronal development
After 1 d in culture, MAP2 appears to be uniformly distributed throughout both axons and dendrites.
“After 1 d in culture, at a time when MAP2 appears to be uniformly distributed throughout both axons and dendrites”
Quote in the paperSubstantial claim - Findingnone given§ Localization of MAP2 at early stages of neuronal development
Only after 3 or 4 d in culture, when axons and dendrites are already quite distinct morphologically, does the loss of axonal MAP2 begin.
“Only after 3 or 4 d in culture, when axons and dendrites are already quite distinct morphologically, does the loss of axonal MAP2 begin.”
Quote in the paperSubstantial claim - Findingown data§ Loss of MAP2 during axonal development
In some cases, axonal MAP2 was restricted to the growth cone and the segment of axon immediately proximal to it.
“In some cases, axonal MAP2 was restricted to the growth cone and the segment of axon immediately proximal to it (Fig. 6).”
Quote in the paperNot a substantial claim - Findingcitation§ Localization of MAP2 at early stages of neuronal development
After 1 d in culture, dendrites elongate about 5 times more slowly than axons.
“the two classes of processes already differ in their growth characteristics, dendrites elongating about 5 x more slowly than the axons (Banker, unpublished observations).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Banker, unpublished observations
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Findingown data§ Loss of MAP2 during axonal development
Throughout this period of development, immunoreactivity for beta-tubulin appeared uniformly distributed in both the axonal and dendritic processes.
“Throughout this period of development, immunoreactivity for beta-tubulin appeared uniformly distributed in both the axonal and dendritic processes.”
Quote in the paperSubstantial claim - Findingown data§ Localization of MAP2 at early stages of neuronal development
The most unexpected finding in this study was the presence of MAP2 in axons during the first few days of their development in culture.
“Without doubt the most unexpected finding in this study was the presence of MAP2 in axons during the first few days of their development in culture.”
Quote in the paperSubstantial claim - Findingown data§ Discussion
Both MAP2 and tubulin were detected in freshly dissociated hippocampal neurons prepared from 18 and 19 d embryos.
“We detected both MAP2 and tubulin in freshly dissociated hippocampal neurons prepared from 18 and 19 d embryos.”
Quote in the paperSubstantial claim - Findingown data§ Discussion
No significant expression of MAP2 was observed in non-neuronal cells at any stage of development in culture, even as early as 1 d after plating.
“We failed to observe significant expression of MAP2 in non-neuronal cells at any stage of development in culture, even as early as 1 d after plating.”
Quote in the paperSubstantial claim - Findingown data§ Loss of MAP2 during axonal development
MAP2 immunoreactivity appears to be present at the base of the axon.
“It may also be noted in Figure 6 that MAP2 immunoreactivity appears to be present at the base of the axon (arrowheads).”
Quote in the paperNot a substantial claim - Findingown data§ Loss of MAP2 during axonal development
In cultures at a comparable stage fixed with methanol or with formaldehyde alone, little or no axonal immunoreactivity for MAP2 could be detected.
“In cultures at a comparable stage that were fixed with methanol or with formaldehyde alone, little or no axonal immunoreactivity for MAP2 could be detected.”
Quote in the paperSubstantial claim - Findingown data§ Loss of MAP2 during axonal development
By about the end of the first week in culture, axonal MAP2 staining had largely disappeared.
“By about the end of the first week in culture, axonal MAP2 staining had largely disappeared.”
Quote in the paperSubstantial claim - Findingcitation§ Localization of MAP2 at early stages of neuronal development
Electron microscopy of hippocampal cells in culture has revealed densely packed microtubules at all stages of dendritic development, extending to the base of the dendritic growth cone.
“Electron microscopy of hippocampal cells in culture has also revealed densely packed microtubules at all stages of dendritic development, extending to the base of the dendritic growth cone (Bartlett and Banker, 1984a, and unpublished observations).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bartlett and Banker, 1984a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Findingcitation§ Organization of microtubules in hippocampal neurons in culture
In hippocampal neurons in culture, it is most common for the axon to arise as a branch from the proximal portion of a dendrite rather than directly from the cell soma.
“In hippocampal neurons in culture it is most common for the axon to arise as a branch from the proximal portion of a dendrite rather than directly from the cell soma (Bartlett and Banker, 1984a).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bartlett and Banker, 1984a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Findingown data§ Localization of MAP2 at early stages of neuronal development
Tubulin was detected by immunocytochemistry in all processes of developing hippocampal neurons, including dendrites at their earliest stage of development.
“We were able to detect tubulin by immunocytochemistry in all of the processes of developing hippocampal neurons, including dendrites at their earliest stage of development.”
Quote in the paperSubstantial claim - Findingown data§ Localization of MAP2 at early stages of neuronal development
At all stages of dendritic development, tubulin immunoreactivity was retained following detergent extraction.
“At all stages of dendritic development, tubulin immunoreactivity was retained following detergent extraction”
Quote in the paperSubstantial claim - Interpretationcitation
The establishment of neuronal polarity, as manifested by molecular differentiation of the axonal and dendritic cytoskeleton, occurs largely under endogenous control, even under culture conditions in which cell interactions are greatly restricted.
“Taken together with earlier results (Cbceres et al., 1984a), these data indicate that the establishment of neuronal polarity, as manifested by the molecular differentiation of the axonal and dendritic cytoskeleton, occurs largely under endogenous control, even under culture conditions in which cell interactions are greatly restricted.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Cbceres et al., 1984a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Rests on an assumption: Cell interactions are greatly restricted under the culture conditions used.
- Interpretationreasoning
MAP2 does not appear to be involved in the determination of neuronal polarity.
“MAP2 does not appear to be involved in the determination of neuronal polarity; processes that initially contain MAP2 may become either axons or dendrites.”
Quote in the paperSubstantial claim - Interpretationcitation§ Introduction
The development of the high degree of anisotropy characteristic of neurons may arise from molecular asymmetries of the cytoskeleton.
“These results support the notion that the development of the high degree of anisotropy characteristic of neurons may arise from molecular asymmetries of the cytoskeleton.”
Quote in the paperSubstantial claim - Premisecitation§ Introduction
Hippocampal pyramidal cells in primary culture reproduce many of the characteristic structural features that distinguish them in situ.
“Unlike continuous nerve cell lines, hippocampal pyramidal cells in primary culture reproduce many of the characteristic structural features that distinguish them in situ.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Banker and Cowan, 1979 source
- cites Bartlett and Banker, 1984a, b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationcitation§ Results
The MAP2 staining in somata and dendrites represents MAP2 that remains associated with the cytoskeleton after extraction with Triton X-100.
“The staining observed in somata and dendrites represents MAP2 that remains associated with the cytoskeleton after extraction with Triton X-100 (Caceres et al., 1984a).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Caceres et al., 1984a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationreasoning
Processes that initially contain MAP2 may become either axons or dendrites.
“MAP2 does not appear to be involved in the determination of neuronal polarity; processes that initially contain MAP2 may become either axons or dendrites.”
Quote in the paperSubstantial claim - Premisecitation§ Distribution of tubulin and MAP2 early in neuronal development
Preliminary electron-microscopic observations show that longitudinally aligned microtubules form the predominant cytoskeletal element in both developing axons and dendrites.
“Preliminary electronmicroscopic observations of hippocampal neurons at this stage show that longitudinally aligned microtubules form the predominant cytoskeletal element in both developing axons and dendrites (Bartlett and Banker, unpublished observations.)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Bartlett and Banker, unpublished observations
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationown data§ Discussion
MAP2 is present in hippocampal neurons at considerably earlier stages of development than have been studied previously.
“Our results show that MAP2 is present in hippocampal neurons at considerably earlier stages of development than have been studied previously.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Discussion
The compartmentalization of MAP2 occurs appropriately in hippocampal cultures.
“Thus, they demonstrate that the compartmentalization of MAP2 occurs appropriately in hippocampal cultures”
Quote in the paperSubstantial claim - Interpretationown data§ Discussion
The expression of MAP2 occurs quite early in neuronal development.
“These observations show that the expression of MAP2 occurs quite early in neuronal development”
Quote in the paperSubstantial claim - Interpretationreasoning§ Discussion
Trophic factors from glial cells are unlikely to play more than a permissive role in the establishment of cytoskeletal compartmentalization.
“but such factors are unlikely to play more than a permissive role in the establishment of cytoskeletal compartmentalization.”
Quote in the paperSubstantial claim - Interpretationcitation§ Loss of MAP2 during axonal development
The MAP2 immunoreactivity at the base of the axon probably represents staining of the dendritic process from which the axon originates.
“Thus, this immunoreactivity probably represents staining of the dendritic process from which the axon originates.”
Quote in the paperNot a substantial claim - Interpretationreasoning§ Discussion
Hippocampal cultures provide a suitable model system for analyzing the role of MAP2 in dendritic development.
“and, hence, that these cultures provide a suitable model system for analyzing the role of MAP2 in dendritic development.”
Quote in the paperSubstantial claim - Interpretationcitation§ Discussion
The distribution of MAP2 and tubulin in older hippocampal cultures parallels their distribution in situ.
“the distribution of MAP2 and tubulin in older hippocampal cultures parallels their distribution in situ (Caceres et al., 1984a, and this report).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Caceres et al., 1984a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationreasoning§ Discussion
The establishment of neuronal polarity in culture can occur independently of cell-cell contact.
“Taken together with previous observations, which show that polyribosomes also become restricted to the somatodendritic domain in the absence of cell-cell contact (Bartlett and Banker, 1984a), these results indicate that the establishment of neuronal polarity in culture can occur independently of cellcell contact.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bartlett and Banker, 1984a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationown data§ Loss of MAP2 during axonal development
Observations of MAP2 distribution during the transition period provide direct evidence that MAP2 is lost by turnover or redistribution.
“Observations of the distribution of MAP2 during this transition period provided direct evidence indicating that MAP2 is lost by turnover or redistribution.”
Quote in the paperSubstantial claim - Interpretationcitation§ Discussion
The localization of MAP2 does not depend on contact with other neurons or with glial cells.
“It clearly does not depend on contact with other neurons or with glial cells (Caceres et al., 1984a).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Caceres et al., 1984a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Discussion
The majority of neurons in the hippocampus at this stage would have undergone their final cell division only 1 or 2 d before this time.
“The majority of neurons in the hippocampus at this stage would have undergone their final cell division only 1 or 2 d before this time (Banker and Cowan, 1977;Schlessinger et al., 1978).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation§ Discussion
MAP2a does not normally appear in the cerebrum until rather late in development, beginning after the second postnatal week.
“Biochemical studies show that MAP2a does not normally appear in the cerebrum until rather late in development, beginning after the second postnatal week (Binder et al., 1984a).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Binder et al., 1984a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationreasoning§ Discussion
When cells are removed from the embryo at this early stage of development, the subsequent localization of MAP2 must largely occur under endogenous control.
“When cells are removed from the embryo at this early stage of development, the subsequent localization of MAP2 must largely occur under endogenous control.”
Quote in the paperSubstantial claim - Premisecitation§ Loss of MAP2 during axonal development
Axons in these cultures most typically arise as branches from the proximal portion of a dendrite, rather than directly from the cell soma.
“Previous light-and electron-microscopic studies have shown that the axons in these cultures most typically arise as branches from the proximal portion of a dendrite, rather than directly from the cell soma (Bartlett and Banker, 1984a).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Bartlett and Banker, 1984a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationreasoning§ Localization of MAP2 at early stages of neuronal development
There is no reason to suppose that MAP2, which is bound to the cytoskeleton in developing dendrites of hippocampal neurons, is not associated with microtubules.
“Thus, from the evidence at hand, there is no reason to suppose that the MAP2, which is bound to the cytoskeleton in the developing dendrites of hippocampal neurons, is not associated with microtubules.”
Quote in the paperSubstantial claim- Rests on an assumption: MAP2 is bound to the cytoskeleton in the developing dendrites of hippocampal neurons.
- Interpretationown data§ Localization of MAP2 at early stages of neuronal development
The presence of MAP2 in a developing neuronal process is not sufficient to determine that it will differentiate as a dendrite.
“In any event, whether or not developing axons contain MAP2 in situ, our results show quite clearly that the presence of MAP2 in a developing neuronal process is not sufficient to determine that it will differentiate as a dendrite.”
Quote in the paperSubstantial claim - Interpretationown data§ Localization of MAP2 at early stages of neuronal development
The retention of tubulin immunoreactivity following detergent extraction suggests the presence of assembled microtubules.
“suggesting the presence of assembled microtubules.”
Quote in the paperSubstantial claim - Premisecitation§ Localization of MAP2 at early stages of neuronal development
Microtubules have been observed by electron microscopy in Purkinje cell dendrites at these stages, although they are few in number.
“and microtubules have been observed by electron microscopy (Altman, 1972;Frankfurter et al., 1983), although they are few in number.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Altman, 1972 source
- cites Frankfurter et al., 1983
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Classified as probably not a substantial claim. 28
- May combine two claims. 35
- The quote only partly states this claim. 1
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ IntroductionThere are molecular differences between microtubules and neurofilaments in different regions of a neuron and in different classes of neurons.
“In addition, recent biochemical and immunocytochemical studies have established that there are molecular differences between the microtubules (Caceres et al., 1984b;Matus et al., 198 1;Vallee, 1982) and neurofilaments (Hirokawa et al., 1984;Shaw et al., 198 1) in different regions of a neuron, and in different classes of neurons (Goldstein et al., 1983).”
Quote in the paperNot a substantial claim1 of 3 sources checked- cites Caceres et al., 1984b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Matus et al., 198 1
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Vallee, 1982 source
May combine two claims.
Premisecitation§ IntroductionMicrotubules are apt to be especially important in neuronal development because they arise early, usually much before neurofilaments, and because they have been implicated in outgrowth of neuronal processes and transport within axons and dendrites.
“In this regard, microtubules are apt to be especially important because they arise early in neuronal development, usually much before neurofilaments (Pachter and Liem, 1984;Peters and Vaughn, 1967;Shaw et al., 1985), and because they have been implicated in a variety of cellular events, including the outgrowth of neuronal processes and the transport of materials within axons and dendrites.”
Quote in the paperSubstantial claim1 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ IntroductionIn a pheochromocytoma cell line (PC12), neurite outgrowth induced by NGF is accompanied by a selective induction of MAP1.
“In a pheochromocytoma cell line (PC12), neurite outgrowth induced by NGF is accompanied by a selective induction of MAP 1 (Greene et al., 1983).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Greene et al., 1983 source
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ IntroductionMAP1 appears to be present in both axons and dendrites.
“By contrast, MAP1 appears to be present in both axons and dendrites (Bloom et al., 1984;Huber and Matus, 1984b).”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites Bloom et al., 1984 source
- cites Huber and Matus, 1984b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ IntroductionMAP2 is preferentially distributed in gray matter.
“This is consistent with its preferential distribution in gray matter, as has been shown biochemically (Vallee, 1982).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Vallee, 1982 source
Classified as probably not a substantial claim.
Premisecitation§ IntroductionVarious components of the neuronal cytoskeleton are crucial for the differentiation, elaboration, and maintenance of axons and dendrites.
“Several lines of evidence indicate that the various components of the neuronal cytoskeleton are crucial for the differentiation, elaboration, and maintenance of axons and dendrites (for reviews, see Lasek et al., 1983;Solomon, 1981;Solomon and Zurn, 198 1).”
Quote in the paperSubstantial claim1 of 3 sources checked- cites Lasek et al., 1983 source
- cites Solomon, 1981 source
The opening discussion (p. 547) reports that disrupting microtubules or microfilaments inhibits extension of axonlike neurites in cultured cells of neuronal origin, and says three cytoskeletal components may participate in the assumption and loss of asymmetric shape. This supports a role in neurite elaboration and retention, but the paper's qualified discussion does not establish that these components are crucial for the differentiation, elaboration, and maintenance of both axons and dendrites generally. (LLM, conf=0.85)
Experimental — accuracy not yet measured - cites Solomon and Zurn, 198 1
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Classified as probably not a substantial claim. May combine two claims.
Premisecitation§ IntroductionDifferent classes of microtubules appear to contain different isotypes of the tubulin subunits, and these different microtubules appear to be compartmentalized within neurons.
“Different classes of microtubules appear to contain different isotypes of the tubulin subunits (Gazes and Bamstable, 1982;Gazes and Sweadner, 1981;Moura Neto et al., 1983), and these different microtubules appear to be compartmentalized within neurons (Cumming et al., 1983).”
Quote in the paperSubstantial claim1 of 3 sources checked- cites Gazes and Bamstable, 1982
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Gazes and Sweadner, 1981
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Moura Neto et al., 1983 source
Moura Neto et al. is cited for the first clause, not the later claim about compartmentalization. The Results section ('Tubulin heterogeneity in virtually pure neuronal cells') and Discussion show multiple tubulin isoforms in neuronal cultures, but do not establish that distinct classes of microtubules contain different isotypes. The Introduction explicitly leaves open whether tubulin heterogeneity reflects different microtubules within individual cells or differences among cells; page numbers are unavailable in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ Distribution of tubulin and MAP2 early in neuronal developmentRings of microtubules have been observed in the growth cones of sensory neurons in culture.
“Rings of microtubules have been observed in the growth cones of sensory neurons in culture (Tsui et al., 1983).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites Tsui et al., 1983 source
The Abstract reports microtubules in the growth cones of cultured embryonic chicken retina neurons. It does not describe rings of microtubules or identify the studied cells as sensory neurons, so those parts of the claim are unsupported by our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Classified as probably not a substantial claim.
Premisecitation§ Organization of microtubules in hippocampal neurons in cultureAn analogous situation occurs in dorsal root ganglion cells, where there are differences in the structure and transport of cytoskeletal elements in the peripheral and central branches of the axon.
“An analogous situation occurs in dorsal root ganglion cells, where there are differences in the structure and transport of cytoskeletal elements in the peripheral and central branches of the axon (Mori et al., 1979;Smith, 1973;Wujek and Lasek, 1983;Zenker et al., 1975).”
Quote in the paperSubstantial claim1 of 3 sources checkedMay combine two claims.
Findingown dataWithin neurons, MAP2 is present in soma and dendrites, but little or no immunostaining is detectable in axons.
“In contrast, MAP2 was preferentially localized to nerve cells; within neurons, MAP2 was present in soma and dendrites, but little or no immunostaining was detectable in axons.”
- Also stated in: § Results · plain
“Both perikarya and dendrites were intensely immunoreactive for MAP2, but little or no reactivity was observed in any of the axonal processes.”
Quote in the paperSubstantial claim- Also stated in: § Results · plain
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown data§ ResultsDendrites in these cultures are thick at the base, taper with distance from the cell body, branch in Y-shaped angles, and are relatively short (roughly 100-250 μm long at this stage).
“The dendrites are thick at the base, taper with increasing distance from the cell body, branch in Y-shaped angles, and are relatively short (roughly loo-250 Mm long at this stage of development).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingcitation§ ResultsIn cultures maintained for 1-5 weeks in vitro, the distinctive appearance of axons and dendrites is readily apparent by light microscopy.
“In cultures that have been maintained for l-5 weeks in vitro, the distinctive appearance of axons and dendrites is readily apparent by LM.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown data§ Distribution of tubulin and MAP2 early in neuronal developmentIn flattened regions of the cell, MAP2 staining sometimes has a filamentous character, and in one neuron MAP2 appeared associated with filamentous structures forming a ring within the growth cone.
“In flattened regions of the cell, the MAP2 staining could sometimes be seen to have a filamentous character.For example, in the neuron shown in Figure 5D, the MAP2 appears to be associated with filamentous structures that form a ring within the body of the growth cone.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown data§ Localization of MAP2 at early stages of neuronal developmentThe loss of MAP2 staining in axons appears to occur in a proximal-to-distal direction, with axonal staining persisting for the longest time in the region of the growth cone.
“The loss in MAP2 staining appears to occur in a proximal-to-distal direction, with axonal staining persisting for the longest time in the region of the growth cone.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data§ Loss of MAP2 during axonal developmentImmunoreactivity for MAP2 at the origin of the axon was also seen following formaldehyde or methanol fixation and persisted at later developmental stages, after MAP2 staining of the distal axon had disappeared.
“Immunoreactivity for MAP2 at the origin of the axon was also seen following formaldehyde or methanol fixation and persisted at later developmental stages, after MAP2 staining of the distal axon had disappeared.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingcitation§ Distribution of tubulin and MAP2 early in neuronal developmentWithin a day after plating, most neurons have begun to extend processes, typically one major process 50-100 μm long and several shorter minor processes.
“Within a day after plating, most neurons had begun to extend processes, as shown in Figure 4. Typically these included one major process, which at this stage was 50-100 pm in length, and several, much shorter, minor processes (see Banker and Cowan, 1977).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Banker and Cowan, 1977 source
The quote only partly states this claim.
Findingown data§ Distribution of tubulin and MAP2 early in neuronal developmentMAP2 immunoreactivity can be followed to the tips of axons as far as 150 μm from the cell bodies after 2 d in culture.
“This was also true following culture for 2 d, when MAP2 immunoreactivity could be followed to the tips of axons as far as 150 pm from the cell bodies.”
Quote in the paperSubstantial claimMay combine two claims.
Findingcitation§ DiscussionMAP2 is preferentially expressed by neurons and becomes preferentially localized to neuronal dendrites in dissociated cell culture, where cell-cell interactions are greatly disrupted.
“It is also significant that MAP2 is preferentially expressed by neurons and becomes preferentially localized to neuronal dendrites in dissociated cell culture, where cell<ell interactions are greatly disrupted.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data§ DiscussionBeta-tubulin is uniformly distributed in axonal and dendritic processes of hippocampal neurons and is present in all classes of non-neuronal cells in these cultures.
“Beta-tubulin appears to be uniformly distributed in the axonal and dendritic processes of hippocampal neurons and is present as well in all of the classes of non-neuronal cells found in these cultures.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data§ Distribution of tubulin and MAP2 early in neuronal developmentIn hippocampal neurons in culture, beta-tubulin immunoreactivity is uniformly distributed throughout the cell, and all processes, both axons and dendrites, are heavily stained from the outset.
“In hippocampal neurons in culture, immunoreactivity for beta-tubulin appeared to be uniformly distributed throughout the cell (Fig. 4B).All of the processes, both axons and dendrites, were from the outset heavily stained following exposure to antibodies against beta-tubulin.”
Quote in the paperSubstantial claimMay combine two claims.
Findingnone given§ Localization of MAP2 at early stages of neuronal developmentVimentin filaments largely disappear from hippocampal neurons during the first week in culture, roughly paralleling the period when MAP2 becomes restricted to dendrites.
“Vimentin filaments largely disappear from hippocampal neurons during the first week in culture, which roughly parallels the period when MAP2 becomes restricted to dendrites.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown data§ Organization of microtubules in hippocampal neurons in cultureIn hippocampal neurons in culture, the parent segment and the branch that maintains a dendritic character contain MAP2, while the other, axonal, branch does not.
“This is just what we have observed (see Fig. 6): the parent segment and the branch that maintains a dendritic character contain MAP2, while the other, axonal, branch does not.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationIn dissociated-cell cultures prepared from embryonic rat hippocampus, neurons establish both axons and dendrites, which differ in geometry, in ultrastructure, and in synaptic polarity.
“In dissociated-cell cultures prepared from.the.embryonic rat hippocampus, neurons establish both axons and dendrites, which differ in geometry, in ultrastructure, and in synaptic polarity.”
- Also stated in: § Introduction · plain
“Most important, they establish two distinct classes of processes that can be identified as axons and dendrites based on their geometry, their ultrastructural features, and their synaptic polarity (Banker and Cowan, 1979;Bartlett and Banker, 1984a, b).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Banker and Cowan, 1979 source
- cites Bartlett and Banker, 1984a, b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Also stated in: § Introduction · plain
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ ResultsAlpha-tubulin is also present in all neuronal processes that develop from hippocampal neurons in culture.
“It has been shown by immunofluorescence microscopy that alpha-tubulin is also present in all of the neuronal processes that develop from hippocampal neurons in culture (Shaw et al., 1985).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Shaw et al., 1985
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone given§ ResultsIdentical results were obtained with both MAP2-specific monoclonal antibodies.
“Identical results were obtained with both MAP2-specific monoclonal antibodies.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ IntroductionAmong the lower molecular weight MAPs, the tau proteins are also differentially distributed.
“Among the lower molecular weight MAPS, there is recent evidence that the “tau” proteins are also differentially distributed (Binder et al., 1984b, Tytell et al., 1984).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Binder et al., 1984b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Tytell et al., 1984 source
Classified as probably not a substantial claim.
Premisecitation§ IntroductionMAP2, one of the two classes of high-molecular-weight MAPs, is preferentially associated with dendritic microtubules.
“For example, immunocytochemical studies show that MAP2, one of the two classes of high-molecular-weight MAPS (HMW-MAPS), is preferentially associated with dendritic microtubules (Caceres et al., 1984b;DeCamilli et al., 1984;Huber and Matus, 1984a).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Caceres et al., 1984b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites DeCamilli et al., 1984
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Huber and Matus, 1984a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ IntroductionHMW-MAPs are present during the initial phases of dendritic development in cerebellar Purkinje cells.
“Bemhardt and Matus (1982) have shown that HMW-MAPS are present during the initial phases of dendritic development in cerebellar Purkinje cells.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Bemhardt and Matus (1982)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ IntroductionThe H subunit of neurofilaments (200 kDa) is present in some axons that develop in culture, as shown by immunocytochemistry, but is undetectable in the dendrites.
“In contrast, the H subunit of neurofilaments (200 kDa) is present in some of the axons that develop in culture, as shown by immunocytochemistry, but is undetectable in the dendrites (Shaw et al., 1985).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Shaw et al., 1985
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Premisecitation§ IntroductionAxons and dendrites that form in culture differ in the molecular composition of their cytoskeletons; MAP2 is restricted to the soma and dendritic processes, as it is in the hippocampus in situ.
“We have recently shown that the axons and dendrites that form in culture also differ in the molecular composition of their cytoskeletons.MAP2 is restricted to the soma and dendritic processes, as it is in the hippocampus in situ (Caceres et al., 1984a).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Caceres et al., 1984a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone given§ Materials and MethodsThe binding specificity of each monoclonal antibody clone was examined by solid-phase enzyme-linked immunoassay, and cross-reactivity to other proteins was tested by reacting the antibodies with electroblots of rat hippocampus or cerebellum.
“The binding specificity of each clone was examined by solid-phase-enzyme-linked immunoassay, and cross-reactivity to other proteins was tested by reacting the antibodies with electroblots of rat hippocampus or cerebellum.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.
Interpretationreasoning§ IntroductionTaken collectively, results suggest an important role for MAPs in neuronal development, but a clear picture of the function MAPs play has not yet emerged.
“Taken collectively these results suggest an important role for MAPS in neuronal development, but because of the different model systems and experimental approaches used, a clear picture of the function MAPS play has not yet emerged.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ IntroductionHMW-MAPs appear only in differentiated neuroblastoma cells, and the biochemical composition of MAPs changes profoundly during brain development.
“Other studies have shown that HMW-MAPS appear only in differentiated neuroblastoma cells (Izant and Macintosh, 1980;Olmsted and Lyon, 198 1) and that the biochemical composition of the MAPS changes profoundly during brain development (Binder et al., 1984a;Burgoyne and Cumming, 1984;Francon et al., 1982;Mareck et al., 1980).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Izant and Macintosh, 1980
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Olmsted and Lyon, 198 1
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Binder et al., 1984a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Classified as probably not a substantial claim. May combine two claims.
Study design and conductnone given§ Immunocytochemical proceduresCultures treated identically except for omission of the primary antibody or pretreated with an excess of purified antigen served as controls.
“Cultures treated identically except for omission of the primary antibody or pretreated with an excess of purified antigen served as controls.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ ResultsDendrites in these cultures contain ribosomes, exhibit spines, and are exclusively postsynaptic.
“EM has shown that these processes contain ribosomes, exhibit spines, and are exclusively postsynaptic (Bartlett and Banker, 1984b).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Bartlett and Banker, 1984b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ Materials and MethodsCo-culture of hippocampal neurons with astroglial cells greatly enhances neuronal survival.
“It has previously been shown that co-culture of hip-pocampal neurons with astroglial cells greatly enhances neuronal survival (Banker, 1980).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Banker, 1980 source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ ResultsAxons in these cultures are long, thin, uniform in diameter, lack ribosomes, and are exclusively presynaptic.
“Axonal processes are long, thin, and quite uniform in diameter.They intersect one another, fasciculate, and form an extensive plexus, so that individual axons cannot be distinguished from small fascicles by LM and axons cannot be followed to their cells of origin.At the electron-microscopic level, the axons lack ribosomes and are exclusively presynaptic (Bartlett and Banker, 1984b).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Bartlett and Banker, 1984b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ IntroductionSome regional differences in microtubules occur early in neuronal development.
“Some of the regional differences in microtubules occur early in neuronal development (Bemhardt and Matus, 1982).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Bemhardt and Matus, 1982
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ DiscussionMAP2 is present in rat cerebellum, telencephalon, and thalamus on postnatal Day 10, the earliest stage yet examined.
“Biochemical studies have shown that MAP2 is present in the rat cerebellum, telencephalon, and thalamus on postnatal Day 10, the earliest stage yet examined (Binder et al., 1984a;Burgoyne and Cumming, 1984).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Binder et al., 1984a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Burgoyne and Cumming, 1984
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ Distribution of tubulin and MAP2 early in neuronal developmentHMW-MAPs are present in cerebellar Purkinje cells as early as 3 d after birth.
“MAPS are present in cerebellar Purkinje cells as early as 3 d after birth (Bernhardt and Matus, 1982).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Bernhardt and Matus, 1982
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Interpretationreasoning§ Distribution of tubulin and MAP2 early in neuronal developmentThe presence of MAP2 and beta-tubulin so soon after plating almost certainly indicates that they were present in situ, and hence that MAP2 appears very early in neuronal development.
“The presence of these proteins so soon after plating almost certainly indicates that they were present in situ, and hence that MAP2 appears very early in neuronal development.”
Quote in the paperSubstantial claim- Rests on an assumption: Proteins detected in neurons 30 min after plating were present in situ rather than synthesized during the 30 min after plating.
May combine two claims.
Premisecitation§ Localization of MAP2 at early stages of neuronal developmentHippocampal neurons do not contain neurofilaments detectable by immunocytochemistry during the first few days in culture, but many cells contain vimentin filaments, which are present in both developing axons and dendrites.
“Although hippocampal neurons do not contain neurofilaments detectable by immunocytochemistry during the first few days in culture, many of the cells contain vimentin filaments, which are present in both developing axons and dendrites (Shaw et al., 1985).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Shaw et al., 1985
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Interpretationown data§ DiscussionThe compartmentalization of MAP2 immunoreactivity occurs in an unexpected way: MAP2 is not selectively excluded from the axon at early stages of axonal outgrowth, but rather is selectively lost from the axon following an initial period when its distribution is uniform throughout the cell.
“Our observations show that the compartmentalization of MAP2 immunoreactivity occurs in an unexpected way: MAP2 is not selectively excluded from the axon at early stages of axonal outgrowth, but rather is selectively lost from the axon following an initial period when its distribution is uniform throughout the cell.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Premisecitation§ DiscussionMAP1 and MAP2 have been detected in cerebellar Purkinje cells on postnatal Day 3, roughly 10 d after Purkinje cell generation; earlier stages were not examined.
“Immunocytochemical studies us-ing a polyclonal antibody that recognizes both MAP 1 and MAP2 have detected these proteins in cerebellar Purkinje cells on postnatal Day 3, roughly 10 d after Purkinje cell generation; earlier stages were not examined (Bernhardt and Matus, 1982).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Bernhardt and Matus, 1982
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Premisecitation§ DiscussionNeurons are quite different from epithelial cells, which become polarized only under culture conditions that permit the establishment of intercellular junctions.
“In this regard neurons are quite different from epithelial cells, which become polarized only under culture conditions that permit the establishment of intercellular junctions (Imhof et al., 1983;Ojakian and Herzlinger, 1984;Sabatini et al., 1983).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Imhof et al., 1983
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Ojakian and Herzlinger, 1984
- cites Sabatini et al., 1983
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ Distribution of tubulin and MAP2 early in neuronal developmentIn cerebellar Purkinje cells, tubulin immunoreactivity cannot be detected at early stages of dendritic outgrowth.
“Bemhardt and Matus (1982) have reported that, in the case of cerebellar Purkinje cells, tubulin immunoreactivity cannot be detected at early stages of dendritic outgrowth.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Bemhardt and Matus (1982)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Premisecitation§ Loss of MAP2 during axonal developmentRetraction of some axonal processes occurs during this stage of axonal development, although many initial axons persist.
“Sequential observation of individual cells has established that retraction of some axonal processes does occur during this stage of axonal development, although many of the initial axons do persist (Banker, unpublished observations).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Banker, unpublished observations
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Premisecitation§ Distribution of tubulin and MAP2 early in neuronal developmentThe axonal arborization arises by continued growth of the major process while many minor processes persist to become the definitive dendrites.
“Sequential photography of individual cells during the first week in culture has shown that the axonal arborization arises by continued growth of the major process while many of the minor processes persist to become the definitive dendrites (Banker, unpublished observations).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Banker, unpublished observations
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Study design and conductown data§ Distribution of tubulin and MAP2 early in neuronal developmentThe beta-tubulin staining in developing dendrites is not attributable solely to unpolymerized tubulin; tubulin immunoreactivity is retained after extraction with Triton X-100 under conditions that remove unpolymerized cytoskeletal subunits but preserve microtubules.
“This staining was not attributable solely to unpolymerized tubulin.Immunofluorescence observations clearly revealed fibrillar staining in the flattened regions from which the dendrites arise, and tubulin immunoreactivity was retained in the developing dendrites following extraction with Triton X-100 under conditions that remove unpolymerized cytoskel-eta1 subunits but preserve microtubules.”
Quote in the paperSubstantial claimMay combine two claims.
Premisecitation§ Localization of MAP2 at early stages of neuronal developmentAt later stages of development, MAP2 is preferentially localized to dendrites, but there appears to be more staining of axons than is seen in the mature brain.
“At later stages of development, MAP2 is preferentially localized to dendrites, but there appears to be more staining of axons than is seen in the mature brain (Frankfurter et al., 1983).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Frankfurter et al., 1983
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Interpretationcitation§ Localization of MAP2 at early stages of neuronal developmentPurkinje cells appear to be exceptional, since microtubules are a prominent element in the developing dendrites of nearly all other types of neurons that have been studied.
“In this regard, Purkinje cells appear to be excep-tional, since microtubules are a prominent element in the developing dendrites of nearly all other types of neurons that have been studied (Miller and Peters, 1981;Peters and Feldman, 1973).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Miller and Peters, 1981
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Peters and Feldman, 1973 source
May combine two claims.
Interpretationreasoning§ Organization of microtubules in hippocampal neurons in cultureSince microtubules in axons and dendrites are different, the two processes arising at such a branch point must contain molecularly distinct populations of microtubules.
“Since the microtubules in axons and dendrites are different, the two processes arising at such a branch point must contain molecularly distinct populations of microtubules.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationreasoning§ Organization of microtubules in hippocampal neurons in cultureEven if axonal and dendritic microtubules arise from two different somatic organizing centers, some additional mechanism would still be required to segregate the two classes of microtubules at such a branch point and to direct the transport of materials produced in the cell body into one or the other branch.
“Even if axonal and dendritic microtubules arise from two different somatic organizing centers, as has been proposed (Lasek and Brady, 1981), some additional mechanism would still be required to segregate the two classes of microtubules at such a branch point and to direct the transport of materials produced in the cell body into one or the other branch.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Lasek and Brady, 1981
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Premisecitation§ Localization of MAP2 at early stages of neuronal developmentTubulin is present in Purkinje cell dendrites at early stages of development, as demonstrated by immunocytochemistry with several monoclonal antibodies.
“Other workers have since demonstrated the presence of tubulin in Purkinje cell dendrites at these stages of development by immunocytochemistry, using several different monoclonal antibodies (Burgoyne and Cumming, 1984;Frankfurter et al., 1983)”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Burgoyne and Cumming, 1984
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Frankfurter et al., 1983
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
The paper relies on this without support.
Cell interactions are greatly restricted under the culture conditions used.
“even under culture conditions in which cell interactions are greatly restricted.”
The paper relies on this without support.
Proteins detected in neurons 30 min after plating were present in situ rather than synthesized during the 30 min after plating.
“The presence of these proteins so soon after plating almost certainly indicates that they were present in situ”
The paper relies on this without support.
The distribution of MAP2 in situ has not yet been studied at comparably early stages.
“The distribution of MAP2 in situ has not yet been studied at comparably early stages.”
The paper relies on this without support.
MAP2 is bound to the cytoskeleton in the developing dendrites of hippocampal neurons.
“the MAP2, which is bound to the cytoskeleton in the developing dendrites of hippocampal neurons, is not associated with microtubules.”
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“, 1983), and microtubules have been observed by electron microscopy (Altman, 1972; Frankfurter et al., 1983), although they are few in number.”
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“The hippocampal neurons in these cultures are in metabolic communication with glial cells, grown on a separate substrate as a source of trophic survival factors (Banker, 1980), but such factors are unlikely to play more than a permissive role in the establishment of cytoskeletal compartmentalization.”
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MAP2 is localized to the dendrites of hippocampal neurons which develop in culture
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Self-citationMICROTUBULES AND FILAMENTS IN THE AXONS AND ASTROCYTES OF EARLY POSTNATAL RAT OPTIC NERVES
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“(Pachter and Liem, 1984; Peters and Vaughn, 1967; Shaw et al., 1985), and because they have been implicated in a variety of cellular events, including the outgrowth of neuronal processes and the transport of materials within axons and dendrites.”
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“They are found along the full length of the dendrites, extending to the base of the dendritic growth cones (Hinds and Hinds, 1972; Skoff and Hamburger, 1974; Vaughn et al., 1974).”
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Self-citationThe differential appearance of neurofilament triplet polypeptides in the developing rat optic nerve
Pachter, J. S., & Liem, R. K. H. (1984) · Developmental Biology · doi:10.1016/0012-1606(84)90021-6 · Cited by 175 · cited 1× · see citing works
“(Pachter and Liem, 1984; Peters and Vaughn, 1967; Shaw et al., 1985), and because they have been implicated in a variety of cellular events, including the outgrowth of neuronal processes and the transport of materials within axons and dendrites.”
BackgroundThe time of origin of neurons in Ammon's horn and the associated retrohippocampal fields
Schlessinger, A. R., Cowan, W. M., & Swanson, L. W. (1978) · Anatomy and Embryology · doi:10.1007/bf00304660 · Cited by 170 · see citing works
Changes in composition and activity of microtubule-associated proteins during brain development
Mareck, A., Fellous, A., Francon, J., & Nunez, J. (1980) · Nature · doi:10.1038/284353a0 · Cited by 160 · see citing works
Heterogeneity of Microtubule‐Associated Proteins and Brain Development
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The cortical plate and molecular layer of the late rat fetus
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Multiple tubulin forms are expressed by a single neurone
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Molecular Biology of Neuronal Geometry: Expression of Neurofilament Genes Influences Axonal Diameter
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Monoclonal antibodies that recognize discrete forms of tubulin.
Gozes, I., & Barnstable, C. J. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.8.2579 · Cited by 115 · see citing works
Reconstruction of dendritic growth cones in neonatal mouse olfactory bulb
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“They are found along the full length of the dendrites, extending to the base of the dendritic growth cones (Hinds and Hinds, 1972; Skoff and Hamburger, 1974; Vaughn et al., 1974).”
BackgroundMicrotubule-associated proteins: subunits of the cytomatrix.
Vallee, R. B., Bloom, G. S., & Theurkauf, W. E. (1984) · The Journal of Cell Biology · doi:10.1083/jcb.99.1.38s · Cited by 106 · see citing works
The dynamic ordering of neuronal cytoskeletons.
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Microheterogeneity ("neurotypy") of neurofilament proteins.
Goldstein, M. E., Sternberger, L. A., & Sternberger, N. H. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.10.3101 · Cited by 103 · cited 1× · see citing works
“, 198 1) in different regions of a neuron, and in different classes of neurons (Goldstein et al., 1983).”
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Self-citationMicroheterogeneity of tubulin proteins in neuronal and glial cells from the mouse brain in culture.
Moura Neto, V., Mallat, M., Jeantet, C., & Prochiantz, A. (1983) · The EMBO Journal · doi:10.1002/j.1460-2075.1983.tb01576.x · Cited by 81 · see citing works
Translocation of the neuronal cytoskeleton and axonal locomotion
Lasek, R. J. (1982) · Philosophical transactions of the Royal Society of London. Series B, Biological sciences · doi:10.1098/rstb.1982.0135 · Cited by 77 · cited 1× · see citing works
“If new MAP2-free microtubules are assembled at the base of the axon during elongation, as other studies suggest (Lasek, 1982), the residual MAP2 would become concentrated in the distal axon.”
BackgroundA microtubule-associated protein specific to differentiated neuroblastoma cells.
Olmsted, J. B., & Lyon, H. D. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)69638-9 · Cited by 77 · see citing works
Specification of cell morphology by endogenous determinants.
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The Axon: A Prototype for Studying Expressional CytoplasmPreprint
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Ultrastructural networks in growth cones and neurites of cultured central nervous system neurons.
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Monoclonal antibodies to the contractile proteins.
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Neurotubules: Different densities in peripheral motor and sensory nerve fibres
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Neurotrophic and Neurotoxic Effects of Amyloid β Protein: Reversal by Tachykinin Neuropeptides
Yankner, B. A., Duffy, L. K., & Kirschner, D. A. (1990) · Science · doi:10.1126/science.2218531 · Cited by 1,975 · see citing works
The establishment of polarity by hippocampal neurons in culture.
Dotti, C., Sullivan, C., & Banker, G. (1988) · The Journal of Neuroscience · doi:10.1523/jneurosci.08-04-01454.1988 · Cited by 1,862 · see citing works
“At this early stage, the processes do not resemble either mature axons or dendrites in shape, and MAP2 is uniformly distributed throughout the cell (Caceres et al., 1986).”
BackgroundMethodResultInfluentialSelf-citationBaas, P. W., Deitch, J. S., Black, M. M., & Banker, G. A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.21.8335 · Cited by 742 · see citing works
Self-citationβ-Amyloid fibrils induce tau phosphorylation and loss of microtubule binding
Busciglio, J., Lorenzo, A., Yeh, J., & Yankner, B. A. (1995) · Neuron · doi:10.1016/0896-6273(95)90232-5 · Cited by 595 · see citing works
Outgrowth-regulating actions of glutamate in isolated hippocampal pyramidal neurons
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Neurotransmitters in the regulation of neuronal cytoarchitecture
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Sánchez, C. (2000) · Progress in Neurobiology · doi:10.1016/s0301-0082(99)00046-5 · Cited by 512 · see citing works
Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice
Dawson, H. N., Ferreira, A., Eyster, M. V., Ghoshal, N., Binder, L. I., & Vitek, M. P. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.6.1179 · Cited by 527 · see citing works
Self-citationThe distribution of synapsin I and synaptophysin in hippocampal neurons developing in culture
Fletcher, T., Cameron, P. L., Camilli, P. V. D., & Banker, G. A. (1991) · Journal of Neuroscience · doi:10.1523/jneurosci.11-06-01617.1991 · Cited by 454 · see citing works
“…to what extent puncta containing synaptic vesicle antigens were restricted to sites of contact between axons and cell bodies or dendrites, we compared the immunofluorescence distribution of synapsin I with that of MAP2, a specific marker for dendrites (DeCamilli et al., 1984; Caceres et al., 1986).”
BackgroundSelf-citationPolarized sorting of viral glycoproteins to the axon and dendrites of hippocampal neurons in culture
Dotti, C. G., & Simons, K. (1990) · Cell · doi:10.1016/0092-8674(90)90240-f · Cited by 427 · see citing works
“Neurosci. abstract, 1982; Caceres et al., 1984,1986; Barlett and Banker, 1964a, 1984b; Shaw et al., 1985; Dotti et al., 1987; Goslin et al., 1988; Banker and Waxman, 1968; Baas et al., 1988).”
BackgroundDevelopment of neuronal polarity: GAP-43 distinguishes axonal from dendritic growth cones
Goslin, K., Schreyer, D. J., Skene, J. H. P., & Banker, G. A. (1988) · Nature · doi:10.1038/336672a0 · Cited by 417 · see citing works
Self-citationExperimental observations on the development of polarity by hippocampal neurons in culture.
Goslin, K., & Banker, G. A. (1989) · The Journal of Cell Biology · doi:10.1083/jcb.108.4.1507 · Cited by 416 · see citing works
“Like their counterparts in situ, the axons and dendrites that develop in embryonic hippocampal cultures differ from one another in light and electron microscopic morphology (Bartlett and Banker, 1984a,b) and in the macromolecular composition of their cytoskeletons and membranous constituents (Shaw et al., 1985; Cacere…”
BackgroundSelf-citationTubulin tyrosination navigates the kinesin-1 motor domain to axons
Konishi, Y., & Setou, M. (2009) · Nature Neuroscience · doi:10.1038/nn.2314 · Cited by 415 · see citing works
Brewer, G. J., & Cotman, C. W. (1989) · Brain Research · doi:10.1016/0006-8993(89)90144-3 · Cited by 376 · see citing works
Drosophila Futsch Regulates Synaptic Microtubule Organization and Is Necessary for Synaptic Growth
Roos, J., Hummel, T., Ng, N., Klämbt, C., & Davis, G. W. (2000) · Neuron · doi:10.1016/s0896-6273(00)81170-8 · Cited by 375 · see citing works
Kosik, K., & Finch, E. (1987) · The Journal of Neuroscience · doi:10.1523/jneurosci.07-10-03142.1987 · Cited by 368 · see citing works
“The work of Caceres et al. (1986) with rat hippocampal cultures describes the progressive loss of MAP2 immunoreactivity in a proximodistal fashion during in vitro development of an axon.”
BackgroundCraig, A. M., Blackstone, C. D., Huganir, R. L., & Banker, G. A. (1993) · Neuron · doi:10.1016/0896-6273(93)90054-u · Cited by 337 · see citing works
Self-citationA Spatial Gradient of Tau Protein Phosphorylation in Nascent Axons
Mandell, J. W., & Banker, G. A. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-18-05727.1996 · Cited by 270 · see citing works
Self-citationGenetically encoded dendritic marker sheds light on neuronal connectivity in Drosophila
Nicolaï, L., Ramaekers, A., Raemaekers, T., Drozdzecki, A., Mauss, A. S., Yan, J., Landgraf, M., Annaert, W. G., & Hassan, B. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010198107 · Cited by 262 · see citing works
Winslow, J. W., Moran, P., Valverde, J., Shih, A., Yuan, J. O., Wong, S. C., Tsai, S. P., Goddard, A. D., Henzel, W. J., Hefti, F. F., et al. (1995) · Neuron · doi:10.1016/0896-6273(95)90335-6 · Cited by 259 · see citing works
Withers, G. S., George, J. M., Banker, G. A., & Clayton, D. F. (1997) · Developmental Brain Research · doi:10.1016/s0165-3806(96)00210-6 · Cited by 235 · see citing works
Self-citationMattson, M. P., & Kater, S. B. (1989) · Brain Research · doi:10.1016/0006-8993(89)91514-x · Cited by 231 · see citing works
Changes in the distribution of GAP-43 during the development of neuronal polarity
Goslin, K., Schreyer, D., Skene, J. H. P., & Banker, G. A. (1990) · Journal of Neuroscience · doi:10.1523/jneurosci.10-02-00588.1990 · Cited by 217 · see citing works
“00/O and dendrites, which, like their counterparts in situ, differ from one another in light and electron microscopic morphology (Bartlett and Banker, 1984a, b), in the macromolecular composition of their cytoskeletal and membranous constituents (Shaw et al., 1985; Caceres et al., 1986; Matus et al., 1986; Goslin et a…”
BackgroundSelf-citationSynaptic localization of a functional NADPH oxidase in the mouse hippocampus
Tejada-Simon, M. V., Serrano, F., Villasana, L., Kanterewicz, B. I., Wu, G., Quinn, M. T., & Klann, E. (2005) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.01.007 · Cited by 203 · see citing works
“Morphologically, dendrites are thick at the base and narrow with increasing distance from the cell body, whereas axonal processes are long, thin, and fairly uniform in diameter (Caceres et al., 1986).”
BackgroundTranslational Machinery in Dendrites of Hippocampal Neurons in Culture
Tiedge, H., & Brosius, J. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-22-07171.1996 · Cited by 205 · see citing works
“When such cultures were double-labeled with an antibody against MAP2 (a protein that is restricted to neuronal cell bodies and dendrites; Cáceres et al., 1986; Goslin et al., 1988), the MAP2 signal in dendrites appeared smooth and continuous, whereas axons remained unlabeled (Fig.”
BackgroundChamak, B., Fellous, A., Glowinski, J., & Prochiantz, A. (1987) · Journal of Neuroscience · doi:10.1523/jneurosci.07-10-03163.1987 · Cited by 206 · see citing works
“One must remain cautious in making this interpretation, however, since Caceres et al. (1986) have shown that MAP2 is present in immature axons and is later redistributed into the dendritic compartment.”
BackgroundTorre, E. R., & Steward, O. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-03-00762.1992 · Cited by 204 · see citing works
“…(1) exhibit the morphological features of dendrites (tapering with distance from the cell body, and at each branch point), (2) stain positively for MAP2 and tubulin (Caceres et al., 1986), and (3) show transport of recently synthesized RNA after pulse labeling with 3H-uridine (Davis et al., 1987).”
BackgroundFletcher, T., Camilli, P. V. D., & Banker, G. A. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-11-06695.1994 · Cited by 204 · see citing works
“Axonal markers such as GAP-43, Ll , and synaptic vesicles are selectively concentrated in the axon at stage 3 of development, but dendritic markers such as MAP2, GABA, receptors, and AMPA-selective glutamate receptors become restricted to the somatodendritic domain only during stage 4 (Caceres et al., 1986; Dotti et a…”
BackgroundSelf-citationEstrogen-enhanced neurite growth: evidence for a selective induction of Tau and stable microtubules
Ferreira, A., & Cáceres, A. (1991) · Journal of Neuroscience · doi:10.1523/jneurosci.11-02-00392.1991 · Cited by 203 · see citing works
Lafanéchère, L., Manier, M., Trigault, N., Pirollet, F., Mazarguil, H., & Job, D. (1994) · Journal of Cell Science · doi:10.1242/jcs.107.6.1529 · Cited by 202 · see citing works
Differential subcellular localization of particular mRNAs in hippocampal neurons in culture
Kleiman, R. J., Banker, G. A., & Steward, O. (1990) · Neuron · doi:10.1016/0896-6273(90)90341-c · Cited by 200 · see citing works
Self-citationDotti, C. G., Banker, G., & Binder, L. (1987) · Neuroscience · doi:10.1016/0306-4522(87)90276-4 · Cited by 199 · see citing works
Self-citationKoldamova, R. P., Lefterov, I. M., Ikonomovic, M. D., Skoko, J., Lefterov, P. I., Isanski, B. A., DeKosky, S. T., & Lazo, J. S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300044200 · Cited by 237 · see citing works
Evidence for the Involvement of Tiam1 in Axon Formation
Kunda, P. E., Paglini, M. G., Quiroga, S., Kosik, K. S., & Cáceres, A. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-07-02361.2001 · Cited by 192 · see citing works
“Dissociated cultures of hippocampal pyramidal cells from embryonic rat brain tissue were prepared as described previously (Cáceres et al., 1986; Mascotti et al., 1997).”
MethodDevelopment and organization of ocular dominance bands in primary visual cortex of the sable ferret
Ruthazer, E. S., Baker, G. E., & Stryker, M. P. (1999) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19990503)407:2 · Cited by 46 · see citing works
Mattson, M. P., Lee, R. E., Adams, M. E., Guthrie, P. B., & Kater, S. B. (1988) · Neuron · doi:10.1016/0896-6273(88)90134-1 · Cited by 178 · see citing works
Dehmelt, L., Smart, F. M., Ozer, R. S., & Halpain, S. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-29-09479.2003 · Cited by 172 · see citing works
“At later stages, MAP2 disappears from axons but is retained in dendrites (Bernhardt and Matus, 1984; Caceres et al., 1986).”
BackgroundNerve growth factor potentiates the neurotoxicity of beta amyloid.
Yankner, B. A., Cáceres, A., & Duffy, L. K. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.22.9020 · Cited by 171 · see citing works
A Regulatory Role for Sphingolipids in Neuronal Growth
Schwarz, A., Rapaport, E., Hirschberg, K., et al. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.18.10990 · Cited by 161 · see citing works
Microtubular reorganization and dendritic growth response in alzheimer's disease
McKee, A. C., Kowall, N. W., & Kosik, K. S. (1989) · Annals of Neurology · doi:10.1002/ana.410260511 · Cited by 159 · see citing works
Input Summation by Cultured Pyramidal Neurons Is Linear and Position-Independent
Cash, S. S., & Yuste, R. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-01-00010.1998 · Cited by 156 · see citing works
“The dendritic identity of the processes was established by MAP2 immunocytochemistry (Caceres et al., 1986).”
Paglini, M. G., Kunda, P. E., Quiroga, S., Kosik, K. S., & Cáceres, A. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.143.2.443 · Cited by 155 · see citing works
“Dissociated cultures of hippocampal pyramidal cells from embryonic rat brain tissue were prepared as described previously (Cáceres et al., 1986; Mascotti et al., 1997).”
MethodMicrotubule dynamics in axons and dendrites
Baas, P. W., Slaughter, T., Brown, A., & Black, M. M. (1991) · Journal of Neuroscience Research · doi:10.1002/jnr.490300115 · Cited by 150 · see citing works
“This is surprising given that the MTs of axons differ from those of dendrites in many respects, and in particular in their complements of microtubule-associated proteins (MAPs) (Binder et al., 1985; Caceres et al., 1986; Peng et al., 1986; Matus, 1988).”
Evidence for the Role of MAP1B in Axon Formation
González-Billault, C. E., Ávila, J., & Cáceres, A. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.7.2087 · Cited by 153 · see citing works
“Dissociated cultures of hippocampal pyramidal cells from embryonic mice brain tissue were then prepared as described previously (Cáceres et al., 1986; Paglini et al., 1998).”
BackgroundMethodLocalization and Mobility of ω-Conotoxin-Sensitive Ca 2+ Channels in Hippocampal CA1 Neurons
Jones, O., Kunze, D. L., & Angelides, K. J. (1989) · Science · doi:10.1126/science.2543080 · Cited by 153 · see citing works
Ferreira, A., Busciglio, J. A., & Cáceres, A. (1989) · Developmental Brain Research · doi:10.1016/0165-3806(89)90023-0 · Cited by 151 · see citing works
Eves, E. M., Tucker, M. S., Roback, J. D., Downen, M., Rosner, M. R., & Wainer, B. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.10.4373 · Cited by 149 · see citing works
Pietrini, G., Matteoli, M., Banker, G. A., & Caplan, M. J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.18.8414 · Cited by 146 · see citing works
Self-citationNeuronal Expression of the Glutamate Transporter GLT-1 in Hippocampal Microcultures
Mennerick, S. J., Dhond, R. P., Benz, A. M., Xu, W., Rothstein, J. D., Danbolt, N. C., Isenberg, K. E., & Zorumski, C. F. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-12-04490.1998 · Cited by 141 · see citing works
“Finally, we also found some examples of GLT-1-positive processes that showed no detectable MAP2 immunoreactivity.”
InfluentialBosi, S., Rauti, R., Laishram, J., Turco, A., Lonardoni, D., Nieus, T. R., Prato, M., Scaini, D., & Ballerini, L. (2015) · Scientific Reports · doi:10.1038/srep09562 · Cited by 139 · see citing works
Abad‐Rodríguez, J., Piddini, E., Hasegawa, T., Miyagi, T., & Dotti, C. G. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-21-08387.2001 · Cited by 138 · see citing works
“These proteins become segregated to axons and dendrites, respectively, not earlier than 4–5 d in culture (Caceres et al., 1984, 1986).”
BackgroundExpression of the Class III β‐tubulin isotype in developing neurons in culture
Ferreira, A., & Cáceres, A. (1992) · Journal of Neuroscience Research · doi:10.1002/jnr.490320407 · Cited by 136 · see citing works
Karchewski, L. A., Kim, F. A., Johnston, J. M., McKnight, R. M., & Verge, V. M. K. (1999) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19991018)413:2 · Cited by 81 · see citing works
Plasticity of Polarization: Changing Dendrites into Axons in Neurons Integrated in Neuronal Circuits
Gomis-Rüth, S., Wierenga, C. J., & Bradke, F. (2008) · Current Biology · doi:10.1016/j.cub.2008.06.026 · Cited by 135 · see citing works
Tombaugh, G. C., Yang, S. H., Swanson, R. A., & Sapolsky, R. M. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb08884.x · Cited by 134 · see citing works
Cytomechanics of neurite outgrowth from chick brain neurons
Chada, S., Lamoureux, P. L., Buxbaum, R. E., et al. (1997) · Journal of Cell Science · doi:10.1242/jcs.110.10.1179 · Cited by 133 · see citing works
Intracellular messengers in the generation and degeneration of hippocampal neuroarchitecture
Mattson, M. P., Guthrie, P. B., & Kater, S. B. (1988) · Journal of Neuroscience Research · doi:10.1002/jnr.490210236 · Cited by 132 · see citing works
Time frame of mitral cell development in the mice olfactory bulb
Blanchart, A., Carlos, J., & López‐Mascaraque, L. (2006) · The Journal of Comparative Neurology · doi:10.1002/cne.20941 · Cited by 131 · see citing works
“4) (Caceres et al., 1986).”
Even in culture, oligodendrocytes myelinate solely axons.
Lubetzki, C., Demerens, C., Anglade, P., Villarroya, H., Frankfurter, A. J., Lee, V. M., & Zalc, B. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.14.6820 · Cited by 129 · see citing works
Arias, C., Sharma, N., Davies, P., & Shafit‐Zagardo, B. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb02172.x · Cited by 127 · see citing works
Diverse Distribution and Function of Fibrous Microtubule-Associated Proteins in the Nervous System
Schoenfeld, T. A., & Obar, R. A. (1994) · International review of cytology · doi:10.1016/s0074-7696(08)62631-5 · Cited by 124 · see citing works
Marquez-Sterling, N. R., Lo, A., Sisodia, S. S., & Koo, E. H. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-01-00140.1997 · Cited by 124 · see citing works
Hikino, M., Mikami, T., Faissner, A., Vilela-Silva, A.-C. E. S., Pavão, M. S. G., & Sugahara, K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308169200 · Cited by 124 · see citing works
Mattson, M. P., & Kater, S. B. (1988) · International Journal of Developmental Neuroscience · doi:10.1016/0736-5748(88)90050-0 · Cited by 124 · see citing works
Lochter, A., & Schachner, M. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-09-03986.1993 · Cited by 123 · see citing works
“However, these latter results are not unsuspected since MAP2 has been found compartmentalized only after several days in culture (Caceres et al., 1986; Chamak and Prochiantz , 1989), and GAP-43 was described as enriched, but not exclusively expressed, in major neurites of early stage 3 neurons…”
ResultA conservedα-herpesvirus protein necessary for axonal localization of viral membrane proteins
Tomishima, M. J., & Enquist, L. W. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.200011146 · Cited by 120 · see citing works
“Many types of neurons can not sort their proteins to axonal or dendritic compartments until at least 2 wk of growth in vitro (Caceres et al., 1986; Goslin et al., 1990; Ledesma et al., 1999).”
BackgroundDevelopment and selective neurodegeneration in cell cultures from different hippocampal regions
Mattson, M. P., & Kater, S. B. (1989) · Brain Research · doi:10.1016/0006-8993(89)90436-8 · Cited by 116 · see citing works
Laurino, L., Wang, X. X., de la Houssaye, B. A., Sosa, L. J., Dupraz, S., Cáceres, A., Pfenninger, K. H., & Quiroga, S. (2005) · Journal of Cell Science · doi:10.1242/jcs.02490 · Cited by 113 · see citing works
“Dissociated hippocampal pyramidal cells were prepared from embryonic rat brain and cultured as described previously (Mascotti et al., 1997; Cáceres et al., 1986).”
MethodLabelle, C., & Leclerc, N. M. (2000) · Developmental Brain Research · doi:10.1016/s0165-3806(00)00069-9 · Cited by 110 · see citing works
Influence of extracellular matrix proteins on the expression of neuronal polarity
Chamak, B., & Prochiantz, A. (1989) · Development · doi:10.1242/dev.106.3.483 · Cited by 110 · see citing works
Mandolesi, G., Madeddu, F., Bozzi, Y., Maffei, L., & Ratto, G. M. (2004) · The FASEB Journal · doi:10.1096/fj.04-1805fje · Cited by 109 · see citing works
Selective enhancement of axonal branching of cultured dentate gyrus neurons by neurotrophic factors
Patel, M., & McNamara, J. O. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00281-m · Cited by 109 · see citing works
Vitek, D. J., Schall, J. D., & Leventhal, A. G. (1985) · The Journal of Comparative Neurology · doi:10.1002/cne.902410102 · Cited by 108 · see citing works
Marchini, A., Raspa, A., Pugliese, R., El Malek, M. A., Pastori, V., Lecchi, M., Vescovi, A. L., & Gelain, F. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1818392116 · Cited by 99 · see citing works
“Moreover, positive cells for βIII-TUB and GFAP markers were evenly distributed inside the construct, from the edges to the core, as could be seen in full-coronal sections of Fig.”
ResultInfluentialTucker, R. P., & Matus, A. I. (1988) · Developmental Biology · doi:10.1016/0012-1606(88)90338-7 · Cited by 107 · see citing works
Harrill, J., Freudenrich, T. M., Machacek, D. W., Stice, S. L., & Mundy, W. R. (2010) · NeuroToxicology · doi:10.1016/j.neuro.2010.02.003 · Cited by 106 · see citing works
“3D), a neuronal microtubule-associated protein enriched in dendrites (Caceres et al., 1986).”
BackgroundAβ1-42 stimulates actin polymerization in hippocampal neurons through Rac1 and Cdc42 Rho GTPases
Mendoza‐Naranjo, A., González-Billault, C. E., & Maccioni, R. B. (2007) · Journal of Cell Science · doi:10.1242/jcs.03323 · Cited by 107 · see citing works
“Sprague-Dawley rats as described previously (Caceres et al., 1986).”
Lein, P. J., Banker, G. A., & Higgins, D. M. (1992) · Developmental Brain Research · doi:10.1016/0165-3806(92)90159-t · Cited by 103 · see citing works
Self-citationDifferentiated neurons retain the capacity to generate axons from dendrites
Bradke, F., & Dotti, C. G. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00807-1 · Cited by 103 · see citing works
“Stage 2 neurons were treated with cytochalasin D or DMSO for 5 days, fixed and stained for the axonal markers Tau-1 and the growth-associated protein 43 (GAP-43) [7,9,10] and the dendritic marker MAP-2 [5].”
BackgroundMethodExtracellular and Intracellular Signaling for Neuronal Polarity
Namba, T., Funahashi, Y., Nakamuta, S., Xu, C., Takano, T., & Kaibuchi, K. (2015) · Physiological Reviews · doi:10.1152/physrev.00025.2014 · Cited by 101 · see citing works
Pietrini, G., Suh, Y. J., Edelmann, L., Rudnick, G., & Caplan, M. J. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)41828-x · Cited by 100 · see citing works
Regulation of membrane expansion at the nerve growth cone
Pfenninger, K. H., Laurino, L., Peretti, D., Wang, X., Rosso, S. B., Morfini, G. A., Cáceres, A., & Quiroga, S. (2003) · Journal of Cell Science · doi:10.1242/jcs.00285 · Cited by 97 · see citing works
“…of differentiation, a neuron was considered to be in stage 3 when the length of one of the processes (the axon) exceeded the average length of the other processes (the minor processes) by at least 20 µm (Cáceres et al., 1986; Dotti et al., 1988); without a discernible axon, neurons were in stage 2.”
BackgroundMethodActivity-dependent Regulation of Dendritic BC1 RNA in Hippocampal Neurons in Culture
Muslimov, I. A., Banker, G. A., Brosius, J., et al. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.7.1601 · Cited by 97 · see citing works
“In addition, to probe for possible effects of TTX on neuronal morphology, we monitored dendritic extent and synapse density of cells in TTX and control cultures using antibodies against dendritic MAP2 (Cáceres et al., 1986) and against synaptophysin (Fletcher et al.”
BackgroundSelf-citationIrving, A. J., Coutts, A. A., Harvey, J., Rae, M. G., Mackie, K., Bewick, G. S., & Pertwee, R. G. (2000) · Neuroscience · doi:10.1016/s0306-4522(00)00120-2 · Cited by 96 · see citing works
Microtubule Dynamics in Neuronal Development, Plasticity, and Neurodegeneration
Penazzi, L., Bakota, L., & Brandt, R. (2015) · International review of cytology · doi:10.1016/bs.ircmb.2015.09.004 · Cited by 94 · see citing works
Regulation of mouse embryonic stem cell neural differentiation by retinoic acid
Kim, M., Habiba, A., Doherty, J. M., Mills, J. C., Mercer, R. W., & Huettner, J. E. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.02.001 · Cited by 94 · see citing works
“Mature neurons exhibit distinct axonal and somatodendritic compartments; the degree of polarity increases with neuronal maturation [Caceres et al., 1986; Dotti et al., 1988].”
BackgroundDeitch, J., & Banker, G. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-10-04301.1993 · Cited by 95 · see citing works
“The differences in microtubule density and in microtubule-associated protein composition between mature axons and dendrites apparently arise later in development, well after polarity is established (see Bartlett and Banker, 1984a,b; Caceres et al., 1986).”
Self-citationRoux, P. L., & Reh, T. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-08-04639.1994 · Cited by 93 · see citing works
The Effects of Ketamine-Isomers on Neuronal Injury and Regeneration in Rat Hippocampal Neurons
Himmelseher, S., Pfenninger, E., & Georgieff, M. (1996) · Anesthesia and Analgesia · doi:10.1097/00000539-199609000-00011 · Cited by 87 · see citing works
“and the maintenance in a serum-free medium (14,15)”
BackgroundMethodInfluentialSeong, E., Wainer, B. H., Hughes, E. D., et al. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e04-10-0892 · Cited by 86 · see citing works
“These neuronal cultures possess a branched and polarized morphology where subcellular domains can be easily identified by cytoskeletal markers (Caceres et al., 1986).”
Aoyagi, A., Nishikawa, K., Saito, H., & Abe, K. (1994) · Brain Research · doi:10.1016/0006-8993(94)91188-6 · Cited by 86 · see citing works
Ferreira, A., Busciglio, J. A., & Cáceres, A. (1987) · Developmental Brain Research · doi:10.1016/0165-3806(87)90191-x · Cited by 86 · see citing works
Saul, A., Sprenger, F., Bayer, T. A., & Wirths, O. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.05.003 · Cited by 85 · see citing works
Abnormal synapse formation in agrin-depleted hippocampal neurons
Ferreira, A. (1999) · Journal of Cell Science · doi:10.1242/jcs.112.24.4729 · Cited by 82 · see citing works
Evidence for the Involvement of Kif4 in the Anterograde Transport of L1-Containing Vesicles
Peretti, D., Peris, L., Rosso, S. B., Quiroga, S., & Cáceres, A. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.149.1.141 · Cited by 81 · see citing works
“Dissociated cultures of hippocampal pyramidal cells from embryonic rat brain tissue were prepared as described previously (Cáceres et al., 1986; Mascotti et al., 1997).”
MethodRegionally specific properties of midbrain glia: I. Interactions with midbrain neurons
Garcia-Abreu, J., Moura‐Neto, V., de Carvalho, S. L., & Cavalcante, L. A. (1995) · Journal of Neuroscience Research · doi:10.1002/jnr.490400406 · Cited by 80 · see citing works
Li, F., Shetty, A. K., & Sugahara, K. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m609296200 · Cited by 77 · see citing works
Ganglioside Synthesis during the Development of Neuronal Polarity
Hirschberg, K., Zisling, R., van Echten‐Deckert, G., & Futerman, A. H. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.25.14876 · Cited by 76 · see citing works
Central neuronal synapse formation on micropatterned surfaces
Ma, W., Liu, Q.-Y., Jung, D. R., et al. (1998) · Developmental Brain Research · doi:10.1016/s0165-3806(98)00142-4 · Cited by 76 · see citing works
- Authors
- Caceres, A., Banker, G., & Binder, L.
- Affiliations
- Albany Medical College (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1986-03-01
- Volume
- 6
- Issue
- 3
- Pages
- 714-722
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6568475
- OpenAlex
- W1604664180
- Semantic Scholar
- 3a607142ce3477d35f9a8980c73254bdc41d664f
- Cited by
- 367
- References
- 39
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2022: 8 · 2021: 8 · 2020: 9 · 2019: 4 · 2018: 3 · 2017: 7 · 2016: 5 · 2015: 14 · 2014: 6 · 2013: 9 · 2012: 3
- FWCI
- 7.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Funders
- National Institutes of Health (NS12333)
- Fogarty International Center
- National Institute of Neurological Disorders and Stroke (NS-12333, NS 17112)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- beta-tubulin, MAP2, hippocampal neurons, neuronal polarity, axon development, dendrite formation, axonal growth cones, cytoskeleton, neuronal differentiation, glial progenitor cells, astrocytes, fibroblasts
- MeSH terms
- Animals, Axons, Dendrites, Female, Hippocampus, Histocytochemistry, Immunologic Techniques, Microtubule-Associated Proteins, Neurons, Pregnancy, Tissue Distribution, Tubulin, Rats
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