The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index; 8 of the 16 sources its claims cite were checked for support.
Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity
Open accessAbstract
One of the first steps in neurogenesis is the diversification of cells along the dorsoventral axis. In Drosophila the central nervous system develops from three longitudinal columns of cells: ventral cells that express the vnd/nk2 homeobox gene, intermediate cells, and dorsal cells that express the msh homeobox gene. Here we describe a new Drosophila homeobox gene, intermediate neuroblasts defective (ind), which is expressed specifically in the intermediate column cells. ind is essential for intermediate column development: Null mutants have a transformation of intermediate to dorsal column neuroectoderm fate, and only 10% of the intermediate column neuroblasts develop. The establishment of dorsoventral column identity involves negative regulation: Vnd represses ind in the ventral column, whereas ind represses msh in the intermediate column. Vertebrate genes closely related to vnd (Nkx2.1 and Nkx2.2), ind (Gsh1 and Gsh2), and msh (Msx1 and Msx3) are expressed in corresponding ventral, intermediate, and dorsal domains during vertebrate neurogenesis, raising the possibility that dorsoventral patterning within the central nervous system is evolutionarily conserved.
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8 of 16 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Similarly msh expression in the dorsal neuroectoderm is mirrored by Msx1 transcription in the dorsal neural tube (D' Alessio and Frasch 1996;Isshiki et al. 1997).”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Parallels with vertebrate neural patterning The vertebrate CNS develops from a dorsal neuroepithelium that is similar in many respects to the Drosophila ventral neuroectoderm.For example, in Xenopus the neural primordium is established by Chordin-mediated repression of BMP4 activity, whereas in Drosophila, the Chordin homolog Sog inhibits the BMP4 homolog Dpp to establish the neuroectoderm (for review, see Ferguson 1996;Bier 1997).In addition vertebrate orthologs of vnd and msh have been identified: Nkx2.1 and Nkx2.2 and Msx1 and Msx3, respectively (Holland 1991;Barth and Wilson 1995).Like vnd expression, Nkx2.2 expression is restricted to ventral regions of the nerve cord in the regions that give rise to motor neurons (Fig. 7).Similarly msh expression in the dorsal neuroectoderm is mirrored by Msx1 transcription in the dorsal neural tube (D' Alessio and Frasch 1996;Isshiki et al. 1997).The similar spatial distribution of Nkx2.2 and Msx1 and Msx3 expression to that of vnd and msh, respectively suggests a conserved mechanism of DV patterning across species (D' Alessio and Frasch 1996;Wang et al. 1996).Consistent with this, a putative ind ortholog, Gsh1, is expressed in symmetric lateral domains in the mouse neural tube (Fig. 7; Valerius et al. 1995).In Figure 7 the DV order of the Drosophila and mouse genes are clearly the same.It is also apparent that there are gaps between the expression domains of the three vertebrate genes that we have compared.We speculate that other related vertebrate genes will fill in these gaps.If the overall parallel is indicative of an evolutionary relationship, it will be of great importance to investigate what target genes might be regulated in common by the fly and vertebrate genes.Common targets might be revealing about ancient cell type diversification during neurogenesis.
What the sources say
- Supportedcites D' Alessio and Frasch 1996 source
Section 3.3 says msh and its vertebrate homologs occupy topologically similar positions in the Drosophila neuroectoderm and vertebrate neural plate or tube. The Fig. 10 caption makes the comparison explicit: Msx1 is expressed in the dorsal neural tube, with an expression boundary analogous to that of Drosophila msh. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites Isshiki et al. 1997 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Vertebrate genes closely related to vnd (Nkx2.1 and Nkx2.2), ind (Gsh1 and Gsh2), and msh (Msx1 and Msx3) are expressed in corresponding ventral, intermediate, and dorsal domains during vertebrate neurogenesis”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Abstract
What the sources say
- Partly supportedcites Valerius et al. 1995 sourceExperimental — accuracy not yet measured
The In Situ Hybridizations section reports Gsh-1 expression in a restricted mid-ventricular region of the developing mouse neural tube, supporting the intermediate-domain portion of the claim. The Gsh-1 Target DNA Binding Sequence section also reports strong Gsh-1/Gsh-2 homeodomain similarity. Our copy does not establish the proposed relationships to ind, vnd, or msh, or the claimed ventral and dorsal expression patterns of the other listed genes; the passages provide no page numbers. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites Szucsik et al. 1997 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The Ind proteincontaining cells are immediately adjacent but nonoverlapping with Vnd-containing cells of the ventral column neuroectoderm (see McDonald et al. 1998).”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > A screen for genes regulated by Tinman class homeodomain proteins
What the sources say
- Supportedcites McDonald et al. 1998 source
The Figure 3 caption says that, in wild-type embryos, Ind expression is restricted to the intermediate column neuroectoderm, while the Vnd protein section places Vnd in the ventral column neuroectoderm. The paper also describes Ind-positive cells directly abutting Vnd-positive cells without expressing Vnd. (LLM, conf=0.91)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The similar spatial distribution of Nkx2.2 and Msx1 and Msx3 expression to that of vnd and msh, respectively suggests a conserved mechanism of DV patterning across species (D' Alessio and Frasch 1996;Wang et al. 1996).”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Parallels with vertebrate neural patterning The vertebrate CNS develops from a dorsal neuroepithelium that is similar in many respects to the Drosophila ventral neuroectoderm.For example, in Xenopus the neural primordium is established by Chordin-mediated repression of BMP4 activity, whereas in Drosophila, the Chordin homolog Sog inhibits the BMP4 homolog Dpp to establish the neuroectoderm (for review, see Ferguson 1996;Bier 1997).In addition vertebrate orthologs of vnd and msh have been identified: Nkx2.1 and Nkx2.2 and Msx1 and Msx3, respectively (Holland 1991;Barth and Wilson 1995).Like vnd expression, Nkx2.2 expression is restricted to ventral regions of the nerve cord in the regions that give rise to motor neurons (Fig. 7).Similarly msh expression in the dorsal neuroectoderm is mirrored by Msx1 transcription in the dorsal neural tube (D' Alessio and Frasch 1996;Isshiki et al. 1997).The similar spatial distribution of Nkx2.2 and Msx1 and Msx3 expression to that of vnd and msh, respectively suggests a conserved mechanism of DV patterning across species (D' Alessio and Frasch 1996;Wang et al. 1996).Consistent with this, a putative ind ortholog, Gsh1, is expressed in symmetric lateral domains in the mouse neural tube (Fig. 7; Valerius et al. 1995).In Figure 7 the DV order of the Drosophila and mouse genes are clearly the same.It is also apparent that there are gaps between the expression domains of the three vertebrate genes that we have compared.We speculate that other related vertebrate genes will fill in these gaps.If the overall parallel is indicative of an evolutionary relationship, it will be of great importance to investigate what target genes might be regulated in common by the fly and vertebrate genes.Common targets might be revealing about ancient cell type diversification during neurogenesis.
What the sources say
- Supportedcites D' Alessio and Frasch 1996 source
Figure 10 describes Msx1 and Msx3 in lateral regions corresponding to Drosophila msh, and Nkx2.2 in a medial region similar to the vnd expression domain. Section 3.3 interprets these spatial similarities as evidence of conserved neural patterning between Drosophila and vertebrates. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites Wang et al. 1996 source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“The three sites protected in the footprinting assay each contain one copy of the sequence GTGAACT, which has been found to be a recognition sequence for both Vnd and the Tinman-related Nkx2.5 vertebrate protein (Chen and Schwartz 1995;Gruschus et al. 1997).”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > A screen for genes regulated by Tinman class homeodomain proteins
What the sources say
- Could not verifycites Chen and Schwartz 1995 sourceExperimental — accuracy not yet measured
The DNA-binding results and Discussion (page unavailable) identify nkx-2.5 binding sequences, including the preferred consensus 5′-CTNNAGTG-3′. Our copy does not report three Vnd sites, a footprinting assay of those sites, or the sequence GTGAACT; searches for GTGAACT and Vnd found no passage addressing the claim. (LLM, conf=0.76)
- Not checked — no full text of the sourcecites Gruschus et al. 1997 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Consistent with this, a putative ind ortholog, Gsh1, is expressed in symmetric lateral domains in the mouse neural tube (Fig. 7; Valerius et al. 1995).”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Parallels with vertebrate neural patterning The vertebrate CNS develops from a dorsal neuroepithelium that is similar in many respects to the Drosophila ventral neuroectoderm.For example, in Xenopus the neural primordium is established by Chordin-mediated repression of BMP4 activity, whereas in Drosophila, the Chordin homolog Sog inhibits the BMP4 homolog Dpp to establish the neuroectoderm (for review, see Ferguson 1996;Bier 1997).In addition vertebrate orthologs of vnd and msh have been identified: Nkx2.1 and Nkx2.2 and Msx1 and Msx3, respectively (Holland 1991;Barth and Wilson 1995).Like vnd expression, Nkx2.2 expression is restricted to ventral regions of the nerve cord in the regions that give rise to motor neurons (Fig. 7).Similarly msh expression in the dorsal neuroectoderm is mirrored by Msx1 transcription in the dorsal neural tube (D' Alessio and Frasch 1996;Isshiki et al. 1997).The similar spatial distribution of Nkx2.2 and Msx1 and Msx3 expression to that of vnd and msh, respectively suggests a conserved mechanism of DV patterning across species (D' Alessio and Frasch 1996;Wang et al. 1996).Consistent with this, a putative ind ortholog, Gsh1, is expressed in symmetric lateral domains in the mouse neural tube (Fig. 7; Valerius et al. 1995).In Figure 7 the DV order of the Drosophila and mouse genes are clearly the same.It is also apparent that there are gaps between the expression domains of the three vertebrate genes that we have compared.We speculate that other related vertebrate genes will fill in these gaps.If the overall parallel is indicative of an evolutionary relationship, it will be of great importance to investigate what target genes might be regulated in common by the fly and vertebrate genes.Common targets might be revealing about ancient cell type diversification during neurogenesis.
What the sources say
- Partly supportedcites Valerius et al. 1995 sourceExperimental — accuracy not yet measured
The In Situ Hybridizations section and Fig. 4 caption report two bilaterally symmetrical stripes of Gsh-1 expression extending along the mouse neural tube; the thoracic section places expression in a restricted mid-ventricular region. The passages do not identify Gsh-1 as a putative ind ortholog, so that part of the claim is not supported by our copy. (LLM, conf=0.86)
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The position of each of the two symmetric ind columns is just dorsal to the domain of vnd transcription (Fig. 4, below), in cells that will become the intermediate column of neuroectoderm.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > A screen for genes regulated by Tinman class homeodomain proteins
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The earliest ind phenotype is observed in stage 7 embryonic neuroectoderm, when msh expression occurs both in its normal locations in the dorsal columns and in the adjacent intermediate columns (Fig. 6A,B).”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > A screen for genes regulated by Tinman class homeodomain proteins
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ind is essential for intermediate column development: Null mutants have a transformation of intermediate to dorsal column neuroectoderm fate, and only 10% of the intermediate column neuroblasts develop.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Vnd is produced in the ventral neuroectoderm immediately adjacent to the ind-expression domain.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > A screen for genes regulated by Tinman class homeodomain proteins
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Probably not a substantial claim. 4
- It may state two separate claims as one. 22
- The quote only partly states this claim. 2
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Similarly, vnd is thought to promote neuroblast formation by proneural-dependent and proneural-independent pathways (Jimenez et. al. 1995;McDonald et al. 1998).”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > ind promotes intermediate-column neuroblast formation
What the sources say
- Not checked — no full text of the sourcecites Jimenez et. al. 1995 source
- Partly supportedcites McDonald et al. 1998 sourceExperimental — accuracy not yet measured
In “Vnd expression during neurogenesis” (page unavailable), the paper proposes that vnd acts with the proneural genes achaete and scute and says it has an additional role beyond activating their expression. It does not establish that this additional role is independent of proneural genes altogether; the passage also mentions lethal of scute in other ventral neuroblasts. (LLM, conf=0.82)
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
Every source the paper cites for this claim was checked and supports it.
In the paper
“In this paper and in McDonald et al. (1998) we show that vnd function is required to establish the ventral border of ind: In the absence of vnd, expression of ind is observed in the ventral-column neuroectoderm and neuroblasts.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Regulation of ind expression along the DV axis of the CNS
What the sources say
- Supportedcites McDonald et al. 1998 source
The section “Loss of vnd transforms ventral to intermediate column identity” reports that, in vnd embryos, Ind is detected in ventral-column neuroectoderm and neuroblasts. The “Vnd expression during neurogenesis” section explicitly says vnd is required to keep ind expression out of those ventral-column cells, supporting the claimed role in establishing ind’s ventral border. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whole-mount in situ hybridization first detects ind expression in two parallel, lateral columns in stage 5 cel-lular blastoderm embryos (Fig. 2).”
- Also stated in: § A screen for genes regulated by Tinman class homeodomain proteins · plain
“During gastrulation, the ind expression domain narrows until each column is two cells wide.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > A screen for genes regulated by Tinman class homeodomain proteins
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § A screen for genes regulated by Tinman class homeodomain proteins · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Embryos lacking ind function have profound defects in the development of the intermediate column of the CNS.”
- Also stated in: § Discussion · plain
“The defects include a derepression of dorsal column markers within the intermediate-column neuroectoderm.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By stage 9, ind mRNA is absent from the neuroectoderm, but is detectable in all of the neuroblasts in the intermediate column (Nbs 3-2, 4-2, 5-3, 6-2, and 7-2).”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > A screen for genes regulated by Tinman class homeodomain proteins
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we describe a new Drosophila homeobox gene, intermediate neuroblasts defective (ind), which is expressed specifically in the intermediate column cells.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In stage 9 wild-type embryos, five neuroblasts constitute the intermediate column in each hemisegment.”
- Also stated in: § ind promotes intermediate-column neuroblast formation · plain
“In ind mutant embryos, at most one intermediate-column neuroblast is observed in each hemisegment, whereas the normal number of ventral and dorsal column neuroblasts form.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > ind promotes intermediate-column neuroblast formation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § ind promotes intermediate-column neuroblast formation · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A total of 80 hemisegments were scored.In a wild-type embryo 400 intermediate neuroblasts would be expected.In the ind mutant embryo 32 were observed.Eleven expressed Vnd, 12 expressed Msh, and 9 expressed neither marker.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > A screen for genes regulated by Tinman class homeodomain proteins
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In wild-type embryos, an Eve-protein-containing RP2 is found in every hemisegment (100/100), whereas in ind mutant embryos the Eve-containing RP2 is never detected (0/96) (Fig. 6M,N).”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > A screen for genes regulated by Tinman class homeodomain proteins
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The Ind protein is detected in the nucleus at all stages assayed, as expected for a homeodomain protein (Fig. 3).”
- Also stated in: § A screen for genes regulated by Tinman class homeodomain proteins · boosted
“The antibody staining confirms that Ind is restricted to the intermediate column neuroectoderm and neuroblasts.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > A screen for genes regulated by Tinman class homeodomain proteins
Strength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one. The quote only partly states this claim.
- Also stated in: § A screen for genes regulated by Tinman class homeodomain proteins · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Vnd specifically binds the fragment of ind genomic DNA isolated in the screen (Fig. 5A).”
- Also stated in: § A screen for genes regulated by Tinman class homeodomain proteins · plain
“Three specific binding sites of roughly equal affinity can be identified using footprinting assays (Fig. 5B).”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > A screen for genes regulated by Tinman class homeodomain proteins
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § A screen for genes regulated by Tinman class homeodomain proteins · plain
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In Figure 7 the DV order of the Drosophila and mouse genes are clearly the same.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Parallels with vertebrate neural patterning The vertebrate CNS develops from a dorsal neuroepithelium that is similar in many respects to the Drosophila ventral neuroectoderm.For example, in Xenopus the neural primordium is established by Chordin-mediated repression of BMP4 activity, whereas in Drosophila, the Chordin homolog Sog inhibits the BMP4 homolog Dpp to establish the neuroectoderm (for review, see Ferguson 1996;Bier 1997).In addition vertebrate orthologs of vnd and msh have been identified: Nkx2.1 and Nkx2.2 and Msx1 and Msx3, respectively (Holland 1991;Barth and Wilson 1995).Like vnd expression, Nkx2.2 expression is restricted to ventral regions of the nerve cord in the regions that give rise to motor neurons (Fig. 7).Similarly msh expression in the dorsal neuroectoderm is mirrored by Msx1 transcription in the dorsal neural tube (D' Alessio and Frasch 1996;Isshiki et al. 1997).The similar spatial distribution of Nkx2.2 and Msx1 and Msx3 expression to that of vnd and msh, respectively suggests a conserved mechanism of DV patterning across species (D' Alessio and Frasch 1996;Wang et al. 1996).Consistent with this, a putative ind ortholog, Gsh1, is expressed in symmetric lateral domains in the mouse neural tube (Fig. 7; Valerius et al. 1995).In Figure 7 the DV order of the Drosophila and mouse genes are clearly the same.It is also apparent that there are gaps between the expression domains of the three vertebrate genes that we have compared.We speculate that other related vertebrate genes will fill in these gaps.If the overall parallel is indicative of an evolutionary relationship, it will be of great importance to investigate what target genes might be regulated in common by the fly and vertebrate genes.Common targets might be revealing about ancient cell type diversification during neurogenesis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“(C,G) Early stage 9 embryos in which ind is expressed in the intermediate neurectoderm and S1, intermediate column neuroblasts.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Antibody generation and immunocytochemistry Rat serum and monoclonal antibodies were raised against an Ind peptide conjugated to bovine serum albumin (BSA).After the monoclonal fusion, hybridoma supernatants were screened by ELISA against a peptide-KLH conjugate.Positive hybridoma lines were tested by immunohistochemistry. Embryo fixation, antibody staining, and identification of homozygous mutant embryos were performed essentially as by McDonald and Doe (1997).Embryos were staged according to Campos-Ortega and Hartenstein (1997).Primary antibodies were used at the following dilutions: mouse anti-Achaete monoclonal (990E5F1; 1:10; Skeath and Carroll 1992), rabbit anti- galactosidase serum (1:3000; Cappel), rat anti--galactosidase monoclonal (1:10; Srinivasan et al. 1998), mouse anti-Eve [2B8; 1:10; (Patel 1994)], rabbit anti-Msh serum (1:500; T. Isshiki and A. Nose, unpubl.),rat anti-Ind serum (1:500), rat anti-IndN1 monoclonal (1:1), and rabbit anti-Vnd serum (1:10).Secondary antibodies of the appropriate species conjugated to biotin (Vector Labs) or alkaline phosphatase (Southern Biotechnology Associates) were used at a dilution of 1:400.Histochemical detection of primary antibodies was done with the HRP Vectastain Elite kit (Vector Labs) in conjunction with the Renaissance TSA Indirect kit (NEN Life Sciences) for some antibodies.After staining, embryos were dissected, mounted in 70% or 85% glycerol and examined on a Zeiss Axioplan microscope.Images were captured with a Sony DKC-5000 digital camera. Figure: 6 These authors contributed equally to this paper.7 Present address: Institutes of Neuroscience, University of Oregon, Eugene, Oregon 97403 USA.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“(B,D,F).ind 16.2 mutant embryos show Msh is expanded in the neurectoderm at stage 7 (B).This persists until stage 9 when the neuroblasts delaminate (D,F).”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Antibody generation and immunocytochemistry Rat serum and monoclonal antibodies were raised against an Ind peptide conjugated to bovine serum albumin (BSA).After the monoclonal fusion, hybridoma supernatants were screened by ELISA against a peptide-KLH conjugate.Positive hybridoma lines were tested by immunohistochemistry. Embryo fixation, antibody staining, and identification of homozygous mutant embryos were performed essentially as by McDonald and Doe (1997).Embryos were staged according to Campos-Ortega and Hartenstein (1997).Primary antibodies were used at the following dilutions: mouse anti-Achaete monoclonal (990E5F1; 1:10; Skeath and Carroll 1992), rabbit anti- galactosidase serum (1:3000; Cappel), rat anti--galactosidase monoclonal (1:10; Srinivasan et al. 1998), mouse anti-Eve [2B8; 1:10; (Patel 1994)], rabbit anti-Msh serum (1:500; T. Isshiki and A. Nose, unpubl.),rat anti-Ind serum (1:500), rat anti-IndN1 monoclonal (1:1), and rabbit anti-Vnd serum (1:10).Secondary antibodies of the appropriate species conjugated to biotin (Vector Labs) or alkaline phosphatase (Southern Biotechnology Associates) were used at a dilution of 1:400.Histochemical detection of primary antibodies was done with the HRP Vectastain Elite kit (Vector Labs) in conjunction with the Renaissance TSA Indirect kit (NEN Life Sciences) for some antibodies.After staining, embryos were dissected, mounted in 70% or 85% glycerol and examined on a Zeiss Axioplan microscope.Images were captured with a Sony DKC-5000 digital camera. Figure: 6 These authors contributed equally to this paper.7 Present address: Institutes of Neuroscience, University of Oregon, Eugene, Oregon 97403 USA.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A P-element insertion obtained from the Drosophila Genome Project was mapped near the coding sequence of ind (Fig. 1).”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Isolation of mutants
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The coding sequence for ind is contained in a single exon, shown as a large box.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Antibody generation and immunocytochemistry Rat serum and monoclonal antibodies were raised against an Ind peptide conjugated to bovine serum albumin (BSA).After the monoclonal fusion, hybridoma supernatants were screened by ELISA against a peptide-KLH conjugate.Positive hybridoma lines were tested by immunohistochemistry. Embryo fixation, antibody staining, and identification of homozygous mutant embryos were performed essentially as by McDonald and Doe (1997).Embryos were staged according to Campos-Ortega and Hartenstein (1997).Primary antibodies were used at the following dilutions: mouse anti-Achaete monoclonal (990E5F1; 1:10; Skeath and Carroll 1992), rabbit anti- galactosidase serum (1:3000; Cappel), rat anti--galactosidase monoclonal (1:10; Srinivasan et al. 1998), mouse anti-Eve [2B8; 1:10; (Patel 1994)], rabbit anti-Msh serum (1:500; T. Isshiki and A. Nose, unpubl.),rat anti-Ind serum (1:500), rat anti-IndN1 monoclonal (1:1), and rabbit anti-Vnd serum (1:10).Secondary antibodies of the appropriate species conjugated to biotin (Vector Labs) or alkaline phosphatase (Southern Biotechnology Associates) were used at a dilution of 1:400.Histochemical detection of primary antibodies was done with the HRP Vectastain Elite kit (Vector Labs) in conjunction with the Renaissance TSA Indirect kit (NEN Life Sciences) for some antibodies.After staining, embryos were dissected, mounted in 70% or 85% glycerol and examined on a Zeiss Axioplan microscope.Images were captured with a Sony DKC-5000 digital camera. Figure: 6 These authors contributed equally to this paper.7 Present address: Institutes of Neuroscience, University of Oregon, Eugene, Oregon 97403 USA.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“(B) Electrophoresis mobilityshift assay using ind DNA nucleotides 5-135, which includes all three Vnd-binding regions.A DNA/protein complex is observed upon addition of Vnd.This complex can be competed out with increasing amounts of the Vnd-I oligonucleotide but not with an irrelevant oligonucleotide (H2A).”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Antibody generation and immunocytochemistry Rat serum and monoclonal antibodies were raised against an Ind peptide conjugated to bovine serum albumin (BSA).After the monoclonal fusion, hybridoma supernatants were screened by ELISA against a peptide-KLH conjugate.Positive hybridoma lines were tested by immunohistochemistry. Embryo fixation, antibody staining, and identification of homozygous mutant embryos were performed essentially as by McDonald and Doe (1997).Embryos were staged according to Campos-Ortega and Hartenstein (1997).Primary antibodies were used at the following dilutions: mouse anti-Achaete monoclonal (990E5F1; 1:10; Skeath and Carroll 1992), rabbit anti- galactosidase serum (1:3000; Cappel), rat anti--galactosidase monoclonal (1:10; Srinivasan et al. 1998), mouse anti-Eve [2B8; 1:10; (Patel 1994)], rabbit anti-Msh serum (1:500; T. Isshiki and A. Nose, unpubl.),rat anti-Ind serum (1:500), rat anti-IndN1 monoclonal (1:1), and rabbit anti-Vnd serum (1:10).Secondary antibodies of the appropriate species conjugated to biotin (Vector Labs) or alkaline phosphatase (Southern Biotechnology Associates) were used at a dilution of 1:400.Histochemical detection of primary antibodies was done with the HRP Vectastain Elite kit (Vector Labs) in conjunction with the Renaissance TSA Indirect kit (NEN Life Sciences) for some antibodies.After staining, embryos were dissected, mounted in 70% or 85% glycerol and examined on a Zeiss Axioplan microscope.Images were captured with a Sony DKC-5000 digital camera. Figure: 6 These authors contributed equally to this paper.7 Present address: Institutes of Neuroscience, University of Oregon, Eugene, Oregon 97403 USA.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Pan neural expression of Hunchback in wild-type late stage 9 embryos shows there are three columns of neuroblasts (K).In ind 16.2 embryos only two columns of S1 neuroblasts are observed.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Antibody generation and immunocytochemistry Rat serum and monoclonal antibodies were raised against an Ind peptide conjugated to bovine serum albumin (BSA).After the monoclonal fusion, hybridoma supernatants were screened by ELISA against a peptide-KLH conjugate.Positive hybridoma lines were tested by immunohistochemistry. Embryo fixation, antibody staining, and identification of homozygous mutant embryos were performed essentially as by McDonald and Doe (1997).Embryos were staged according to Campos-Ortega and Hartenstein (1997).Primary antibodies were used at the following dilutions: mouse anti-Achaete monoclonal (990E5F1; 1:10; Skeath and Carroll 1992), rabbit anti- galactosidase serum (1:3000; Cappel), rat anti--galactosidase monoclonal (1:10; Srinivasan et al. 1998), mouse anti-Eve [2B8; 1:10; (Patel 1994)], rabbit anti-Msh serum (1:500; T. Isshiki and A. Nose, unpubl.),rat anti-Ind serum (1:500), rat anti-IndN1 monoclonal (1:1), and rabbit anti-Vnd serum (1:10).Secondary antibodies of the appropriate species conjugated to biotin (Vector Labs) or alkaline phosphatase (Southern Biotechnology Associates) were used at a dilution of 1:400.Histochemical detection of primary antibodies was done with the HRP Vectastain Elite kit (Vector Labs) in conjunction with the Renaissance TSA Indirect kit (NEN Life Sciences) for some antibodies.After staining, embryos were dissected, mounted in 70% or 85% glycerol and examined on a Zeiss Axioplan microscope.Images were captured with a Sony DKC-5000 digital camera. Figure: 6 These authors contributed equally to this paper.7 Present address: Institutes of Neuroscience, University of Oregon, Eugene, Oregon 97403 USA.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The deletion is 7 kb long and removes the coding sequence for ind.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Antibody generation and immunocytochemistry Rat serum and monoclonal antibodies were raised against an Ind peptide conjugated to bovine serum albumin (BSA).After the monoclonal fusion, hybridoma supernatants were screened by ELISA against a peptide-KLH conjugate.Positive hybridoma lines were tested by immunohistochemistry. Embryo fixation, antibody staining, and identification of homozygous mutant embryos were performed essentially as by McDonald and Doe (1997).Embryos were staged according to Campos-Ortega and Hartenstein (1997).Primary antibodies were used at the following dilutions: mouse anti-Achaete monoclonal (990E5F1; 1:10; Skeath and Carroll 1992), rabbit anti- galactosidase serum (1:3000; Cappel), rat anti--galactosidase monoclonal (1:10; Srinivasan et al. 1998), mouse anti-Eve [2B8; 1:10; (Patel 1994)], rabbit anti-Msh serum (1:500; T. Isshiki and A. Nose, unpubl.),rat anti-Ind serum (1:500), rat anti-IndN1 monoclonal (1:1), and rabbit anti-Vnd serum (1:10).Secondary antibodies of the appropriate species conjugated to biotin (Vector Labs) or alkaline phosphatase (Southern Biotechnology Associates) were used at a dilution of 1:400.Histochemical detection of primary antibodies was done with the HRP Vectastain Elite kit (Vector Labs) in conjunction with the Renaissance TSA Indirect kit (NEN Life Sciences) for some antibodies.After staining, embryos were dissected, mounted in 70% or 85% glycerol and examined on a Zeiss Axioplan microscope.Images were captured with a Sony DKC-5000 digital camera. Figure: 6 These authors contributed equally to this paper.7 Present address: Institutes of Neuroscience, University of Oregon, Eugene, Oregon 97403 USA.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ind appears to be the missing regulator, a gene that precisely marks and controls the development of the intermediate column of neuroectoderm and neuroblasts.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: No genes were known to be expressed specifically in the intermediate column of the Drosophila CNS before this study.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In addition vertebrate orthologs of vnd and msh have been identified: Nkx2.1 and Nkx2.2 and Msx1 and Msx3, respectively (Holland 1991;Barth and Wilson 1995).”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Parallels with vertebrate neural patterning The vertebrate CNS develops from a dorsal neuroepithelium that is similar in many respects to the Drosophila ventral neuroectoderm.For example, in Xenopus the neural primordium is established by Chordin-mediated repression of BMP4 activity, whereas in Drosophila, the Chordin homolog Sog inhibits the BMP4 homolog Dpp to establish the neuroectoderm (for review, see Ferguson 1996;Bier 1997).In addition vertebrate orthologs of vnd and msh have been identified: Nkx2.1 and Nkx2.2 and Msx1 and Msx3, respectively (Holland 1991;Barth and Wilson 1995).Like vnd expression, Nkx2.2 expression is restricted to ventral regions of the nerve cord in the regions that give rise to motor neurons (Fig. 7).Similarly msh expression in the dorsal neuroectoderm is mirrored by Msx1 transcription in the dorsal neural tube (D' Alessio and Frasch 1996;Isshiki et al. 1997).The similar spatial distribution of Nkx2.2 and Msx1 and Msx3 expression to that of vnd and msh, respectively suggests a conserved mechanism of DV patterning across species (D' Alessio and Frasch 1996;Wang et al. 1996).Consistent with this, a putative ind ortholog, Gsh1, is expressed in symmetric lateral domains in the mouse neural tube (Fig. 7; Valerius et al. 1995).In Figure 7 the DV order of the Drosophila and mouse genes are clearly the same.It is also apparent that there are gaps between the expression domains of the three vertebrate genes that we have compared.We speculate that other related vertebrate genes will fill in these gaps.If the overall parallel is indicative of an evolutionary relationship, it will be of great importance to investigate what target genes might be regulated in common by the fly and vertebrate genes.Common targets might be revealing about ancient cell type diversification during neurogenesis.
What the sources say
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We conclude that ind represses msh and achaete gene expression directly or indirectly, and that ind is necessary for establishing proper intermediate-column identity within the neuroectoderm.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > A screen for genes regulated by Tinman class homeodomain proteins
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We believe that the ind phenotype described below is caused specifically by the loss of ind function because the ind 79.3 mutation is a small deficiency that deletes the ind-coding region and 6 kb of flanking DNA, but not any other detectable gene (Fig. 1).”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > A screen for genes regulated by Tinman class homeodomain proteins
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, ind is essential for the formation of intermediate column neuroblasts, and for the repression of ventral-and dorsal-specific genes within these neuroblasts.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > A screen for genes regulated by Tinman class homeodomain proteins
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The three longitudinal columns of cells along the DV axis are defined by the ventral expression and function of vnd; the intermediate expression and function of ind; and the dorsal expression and function of msh.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Regulation of ind expression along the DV axis of the CNS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The sequence of both strands was determined by the cycle sequencing reaction and an automated ABI sequencer (ABI PRISM Dye Terminator Cycle Sequencing Ready Reaction Kit, Perkin Elmer).”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Gene discovery The genomic DNA inserts from the screen were employed as probes in hybridization screening for phage genomic clones by standard protocols (Sambrook et al. 1989).The library screened was provided by John Tamkun (Tamkun et al. 1992).Transcribed regions within the genomic were detected by hybridization to radiolabeled cDNA essentially as in Frei et al. (1986).Restriction digests of DM genomic phage that contained the Tinman binding sites were size fractionated in 0.8% agarose gel and transferred to a nylon filter (Sambrook et al. 1989).The filters were hybridized with radiolabeled cDNA synthesized by random priming of poly(A)-enriched RNA extracted from 0-to 24-hr embryos.Total embryonic RNA was extracted with guanidine HCl and organic solvents as described in Sambrook et al. (1989).Total RNA was enriched for poly(A) + RNA by selection on oligo-dT cellulose according to the manufacturer's directions (Pharmacia, mRNA Purification Kit).Radioactive cDNA was synthesized according to the protocol in Sambrook et al. (1989) with the modification that SuperScript Reverse Transcriptase and Buffers were used (GIBCO-BRL).Hybridization of radioactive cDNA to genomic phage DNA was performed in Church buffer (Church and Gilbert 1984).Fragments of genomic DNA that hybridized to radiolabeled cDNA were employed as probes for whole-mount in situ hybridization to embryos and for hybridization screening of cDNA libraries.Full-length cDNA clones were isolated by standard hybridization screening from the staged embryonic cDNA library of N. Brown (Brown and Kafatos 1988).The sequence of both strands was determined by the cycle sequencing reaction and an automated ABI sequencer (ABI PRISM Dye Terminator Cycle Sequencing Ready Reaction Kit, Perkin Elmer).Homology to known genes was determined by BLAST search of the NCBI database (Altschul et al. 1997).The cytogenetic location of the gene was determined by hybridization to squashes of salivary polytene chromosomes by standard methods (Pardue 1994).
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Loss of ind function results in loss of intermediate-column neuroblasts and intermediate-column-derived neurons.”
§ Dorsoventral patterning in the Drosophila central nervous system: the intermediate neuroblasts defective homeobox gene specifies intermediate column identity > Antibody generation and immunocytochemistry Rat serum and monoclonal antibodies were raised against an Ind peptide conjugated to bovine serum albumin (BSA).After the monoclonal fusion, hybridoma supernatants were screened by ELISA against a peptide-KLH conjugate.Positive hybridoma lines were tested by immunohistochemistry. Embryo fixation, antibody staining, and identification of homozygous mutant embryos were performed essentially as by McDonald and Doe (1997).Embryos were staged according to Campos-Ortega and Hartenstein (1997).Primary antibodies were used at the following dilutions: mouse anti-Achaete monoclonal (990E5F1; 1:10; Skeath and Carroll 1992), rabbit anti- galactosidase serum (1:3000; Cappel), rat anti--galactosidase monoclonal (1:10; Srinivasan et al. 1998), mouse anti-Eve [2B8; 1:10; (Patel 1994)], rabbit anti-Msh serum (1:500; T. Isshiki and A. Nose, unpubl.),rat anti-Ind serum (1:500), rat anti-IndN1 monoclonal (1:1), and rabbit anti-Vnd serum (1:10).Secondary antibodies of the appropriate species conjugated to biotin (Vector Labs) or alkaline phosphatase (Southern Biotechnology Associates) were used at a dilution of 1:400.Histochemical detection of primary antibodies was done with the HRP Vectastain Elite kit (Vector Labs) in conjunction with the Renaissance TSA Indirect kit (NEN Life Sciences) for some antibodies.After staining, embryos were dissected, mounted in 70% or 85% glycerol and examined on a Zeiss Axioplan microscope.Images were captured with a Sony DKC-5000 digital camera. Figure: 6 These authors contributed equally to this paper.7 Present address: Institutes of Neuroscience, University of Oregon, Eugene, Oregon 97403 USA.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The ind mutant alleles used (including the ind79.3 deletion) disrupt only the ind gene, so the observed CNS phenotypes are due to loss of ind function.
The paper relies on this without support.
No genes were known to be expressed specifically in the intermediate column of the Drosophila CNS before this study.
“Although vnd and msh are candidate genes for establishing ventral and dorsal column fates within the CNS, no genes are known currently to be expressed specifically in the intermediate column of the CNS.”
The paper relies on this without support.
The anti-Ind antibodies used specifically detect Ind protein, so the observed protein distribution reflects Ind.
“Rat serum and monoclonal antibodies were raised against an Ind peptide conjugated to bovine serum albumin (BSA).After the monoclonal fusion, hybridoma supernatants were screened by ELISA against a peptide-KLH conjugate.Positive hybridoma lines were tested by immunohistochemistry.”
The paper relies on this without support.
The ind mutant alleles used (including the ind79.3 deletion) disrupt only the ind gene, so the observed CNS phenotypes are due to loss of ind function.
“The deletion is 7 kb long and removes the coding sequence for ind.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
The third P-element mutant has two allele numbers
MinorThe Results identify the third P-element-derived allele as ind 4.1, while Materials and methods identify it as ind 4.2.
“three ind alleles (ind 16.2 , ind 79.3 , and ind 4.1 ) were obtained by mobilizing a P element located next to the ind locus.”
“Additional complementation testing placed two other mutant lines in the same complementation group (ind 79.3 and ind 4.2 ).”
Figure 5 assay panels are reversed in the text
MinorThe Results assign binding and footprinting assays to panels A and B, respectively. The figure caption labels panel A as footprinting and panel B as the mobility-shift binding assay.
“Vnd specifically binds the fragment of ind genomic DNA isolated in the screen (Fig. 5A).Three specific binding sites of roughly equal affinity can be identified using footprinting assays (Fig. 5B).”
“(A) DNase I footprints of both strands of the ind DNA.Three major protected regions become visible as the amount of recombinant Vnd homeodomain is increased.(B) Electrophoresis mobilityshift assay using ind DNA nucleotides 5-135, which includes all three Vnd-binding regions.”
Ind protein is both present and absent after stage 11
MinorThe text says Ind protein is detectable in all intermediate-column neuroblasts at stage 13, but the next sentence says it is not detectable after stage 11.
“In contrast to ind mRNA, Ind protein is detectable in all intermediate column neuroblasts at stage 13, after the mRNA is no longer detectable in most of these neuroblasts.”
“Ind protein is not detectable after stage 11 of embryogenesis.”
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Galliot, B., Quiquand, M., Ghila, L., de Rosa, R., Miljkovic-Licina, M., & Chera, S. (2009) · Developmental Biology · doi:10.1016/j.ydbio.2009.05.563 · Cited by 168
“In Drosophila embryos, the Gsx ortholog named ind is expressed as a longitudinal band in the intermediate neuroectoderm where it promotes activation of proneural genes in the specific set of neuroblasts (Weiss et al., 1998).”
BackgroundInduction of anterior neural fates in the ascidian Ciona intestinalis
Hudson, C., & Lemaire, P. (2001) · Mechanisms of Development · doi:10.1016/s0925-4773(00)00528-1 · Cited by 166
“…Valerius et al., 1995; Hsieh-Li et al., 1995) and subsequently in medaka (Ol-Gsh 1; Deschet et al., 1998), Amphioxus (AmphiGsx; Brooke et al., 1998) and Drosophila (intermediate neuroblasts defective (ind); Weiss et al., 1998) and expression of these molecules is restricted to the nervous system.”
McDonald, J. A., Holbrook, S., Isshiki, T., Weiss, J., Doe, C. Q., & Mellerick, D. M. (1998) · Genes & Development · doi:10.1101/gad.12.22.3603 · Cited by 162
“We use two intermediate column markers: Ind and Huckebein (Chu-LaGraff et al. 1995; McDonald and Doe 1997; Weiss et al. 1998).”
Self-citationVnd/nkx, ind/gsh, and msh/msx: conserved regulators of dorsoventral neural patterning?
Cornell, R. A., & Ohlen, T. L. V. (2000) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(99)00049-5 · Cited by 161
Self-citationThe Capicua repressor – a general sensor of RTK signaling in development and disease
Jiménez, G., Shvartsman, S. Y., & Paroush, Z. (2012) · Journal of Cell Science · doi:10.1242/jcs.092965 · Cited by 158
“…activation in the embryonic neuroectoderm regulates neuroblast differentiation by inducing expression of the intermediate neuroblasts defective (ind) gene, and this occurs, at least in part, through relief of CIC repression (Weiss et al., 1998; von Ohlen et al., 2000; Ajuria et al., 2011) (Fig.”
BackgroundThe hybridoma revolution: an offshoot of basic research
Milstein, C. (1999) · BioEssays · doi:10.1002/(sici)1521-1878(199911)21:11 · Cited by 97
Integration of temporal and spatial patterning generates neural diversity
Erclik, T., Li, X., Courgeon, M., Bertet, C., Chen, Z., Baumert, R., Ng, J., Koo, C., Arain, U., Behnia, R., et al. (2017) · Nature · doi:10.1038/nature20794 · Cited by 146
Lichtneckert, R., & Reichert, H. (2005) · Heredity · doi:10.1038/sj.hdy.6800664 · Cited by 153
“…ventral nerve cord defective (vnd), intermediate neuroblasts defective (ind) and muscle-specific homeobox (msh) are essential for the formation and specification of neuroblasts in the medial, intermediate, and lateral longitudinal columns (Chu et al, 1998; McDonald et al, 1998; Weiss et al, 1998).”
BackgroundA complete temporal transcription factor series in the fly visual system
Konstantinides, N., Holguera, I., Rossi, A. M., Escobar, A., Dudragne, L., Chen, Y., Tran, T. N., Jaimes, A. M. M., Özel, M. N., Simon, F., et al. (2022) · Nature · doi:10.1038/s41586-022-04564-w · Cited by 137
Lu, Z., Sessler, F., Holroyd, N. E., et al. (2016) · Scientific Reports · doi:10.1038/srep31150 · Cited by 145
Marín, Ó., Baker, J., Puelles, L., & Rubenstein, J. L. R. (2002) · Development · doi:10.1242/dev.129.3.761 · Cited by 138
Yu, Z. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki140 · Cited by 136
“The candidate target sequences tested were as follows: the vnd enhancer that directs vnd-specific expression from stage 6 onwards (17), the repression element previously identified in the ind enhancer (6) and a concatenate of seven binding sites corresponding to the consensus NKx2.”
BackgroundInfluentialBuescher, M., Hing, F. S., & Chia, W. (2002) · Development · doi:10.1242/dev.129.18.4193 · Cited by 133
Neuroblast formation and patterning during early brain development in Drosophila
Urbach, R., & Technau, G. M. (2004) · BioEssays · doi:10.1002/bies.20062 · Cited by 136
“described in the vertebrate neural tube, raising the possibility that other genes might fill in these gaps.((80))”
Overton, P. M., Meadows, L. A., Urban, J., & Russell, S. R. H. (2002) · Development · doi:10.1242/dev.129.18.4219 · Cited by 131
Corbin, J. G., Rutlin, M. L., Gaiano, N., & Fishell, G. (2003) · Development · doi:10.1242/dev.00717 · Cited by 131
“Recent analysis indicates that all domains of the telencephalon require at least one of these proteins for the proper development of regional pattern.”
BackgroundOhlen, T. L. V., & Doe, C. Q. (2000) · Developmental Biology · doi:10.1006/dbio.2000.9789 · Cited by 136
Self-citationmsh/Msx gene family in neural development
Ramos, C., & Robert, B. (2005) · Trends in Genetics · doi:10.1016/j.tig.2005.09.001 · Cited by 127
Urbach, R., Schnabel, R., & Technau, G. M. (2003) · Development · doi:10.1242/dev.00528 · Cited by 128
“Similarly, a loss of a few trunk NBs is observed in ind mutants (Weiss et al., 1998).”
BackgroundHalf a century of neural prepatterning: the story of a few bristles and many genes
Gómez-Skármeta, J. L., Campuzano, S., & Modolell, J. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1142 · Cited by 124
Dpp signaling thresholds in the dorsal ectoderm of the Drosophila embryo
Ashe, H. L., Mannervik, M., & Levine, M. (2000) · Development · doi:10.1242/dev.127.15.3305 · Cited by 124
Technau, G. M., Berger, C., & Urbach, R. (2005) · Developmental Dynamics · doi:10.1002/dvdy.20566 · Cited by 123
“These genes promote the formation and/or specify the fate of proneural clusters and NBs along the D/V axis (e.g., Skeath et al., 1994; Isshiki et al., 1997; Chu et al., 1998; McDonald et al., 1998; Skeath, 1998; Udolph et al., 1998; Weiss et al., 1998; Yagi et al., 1998).”
BackgroundCheesman, S. E., Layden, M. J., Ohlen, T. L. V., Doe, C. Q., & Eisen, J. S. (2004) · Development · doi:10.1242/dev.01397 · Cited by 119
“Individual PMNs and VeLD interneurons were labeled using the methods of Eisen et al. (Eisen et al., 1989) and detected with an antifluorescein antibody (1:1000, Boehringer Mannheim).”
BackgroundMethodInfluentialSelf-citationMizutani, C. M., Meyer, N. P., Roelink, H., & Bier, E. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040313 · Cited by 119
“The fact that the zone of ind repression extends considerably further from the dpp stripe than the region of msh activation indicates that msh is not responsible for ind repression, consistent with existing evidence that msh does not regulate ind [9,16].”
BackgroundInfluentialThe contribution of glial cells to Huntington's disease pathogenesis
Wilton, D. K., & Stevens, B. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104963 · Cited by 112
Formation and specification of ventral neuroblasts is controlled by vnd in Drosophila neurogenesisPreprint
Chu, H., Parras, C. M., White, K., & Jiménez, F. (1998) · Genes & Development · doi:10.1101/gad.12.22.3613 · Cited by 113
“…their effect upon localized DER activation in the ventral and intermediate domains (Ip et al. 1992; Golembo et al. 1996; Schnepp et al. 1996), ind in the intermediate domain (Weiss et al. 1998) and msh in the dorsal domain (Isshiki et al. 1997), all affecting Nb formation and/or specification.”
BackgroundInfluentialAllan, D. W., & Thor, S. (2015) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.191 · Cited by 113
EvoD/Vo: the origins of BMP signalling in the neuroectoderm
Mizutani, C. M., & Bier, E. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2417 · Cited by 113
Otx genes in brain morphogenesis
Acampora, D., Gulisano, M., Broccoli, V., & Simeone, A. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00042-3 · Cited by 124
“, 1995) was paralleled by conserved topographical expression (although with inverted D/V polarity) of pairs of homologous genes (NK-2/NK-2.2; ind/Gsh and Msh/Msx ; Arendt and Nübler-Jung, 1996; D’Alessio and Frasch, 1996; Weiss et al., 1998).”
BackgroundInfluentialAshraf, S. I., Hu, X., Roote, J., & Ip, Y. T. (1999) · The EMBO Journal · doi:10.1093/emboj/18.22.6426 · Cited by 110
“This initial determination depends on genes such as ventral nervous system defective (vnd), intermediate neuroblasts defective (ind), muscle segment homeobox (msh) and those in the achaete–scute complex (Isshiki et al., 1997; Campos-Ortega, 1998; Chu et al., 1998; McDonald et al., 1998; Weiss et al., 1998).”
BackgroundUrbach, R., & Technau, G. M. (2003) · Development · doi:10.1242/dev.00532 · Cited by 110
Capicua DNA-binding sites are general response elements for RTK signaling inDrosophila
Ajuria, L., Nieva, C., Winkler, C. J., Kuo, D., Samper, N., Andreu, M. J., Helman, A., González‐Crespo, S., Paroush, Z., Courey, A. J., et al. (2011) · Development · doi:10.1242/dev.057729 · Cited by 105
“Indeed, previous studies have shown that EGFR signaling plays a key role in setting this border (Weiss et al., 1998; von Ohlen and Doe, 2000), and suggested the existence of unknown repressors restricting ind expression in dorsal regions (Stathopoulos and Levine, 2005).”
BackgroundInfluentialInversion of the chordate body axis: Are there alternatives?
Gerhart, J. C. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.9.4445 · Cited by 105
Chiori, R., Jager, M., Denker, E., Wincker, P., Silva, C. D., Guyader, H. L., Manuel, M., & Quéinnec, É. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004231 · Cited by 101
“Since in bilaterians a neural expression of GSX genes is also observed [15,69–70,76–78], GSX is the only Hox-extended gene group showing clear conservation of expression characteristics between cnidarians and bilaterians.”
BackgroundWalsh, K. T., & Doe, C. Q. (2017) · Development · doi:10.1242/dev.157826 · Cited by 103
“…2013; Yu et al., 2013), a neuropil devoted to multimodal sensory processing and locomotion (Martin et al., 1999; Renn et al., 1999; Strauss, 2002; Wessnitzer and Webb, 2006; Poeck et al., 2008; Wang et al., 2008; Pan et al., 2009; Bender et al., 2010; Boyan and Reichert, 2011; Ofstad et al.,…”
Self-citationCharacterization of Homo- and Heterodimerization of Cardiac Csx/Nkx2.5 Homeoprotein
Kasahara, H., Usheva, A., Ueyama, T., Aoki, H., Horikoshi, N., & Izumo, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m004995200 · Cited by 94
Developmental genetic evidence for a monophyletic origin of the bilaterian brain
Reichert, H., & Simeone, A. (2001) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2001.0972 · Cited by 94
Control of neurogenesis — lessons from frogs, fish and flies
Chitnis, A. B. (1999) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(99)80003-8 · Cited by 91
Ashraf, S. I., & Ip, Y. T. (2001) · Development · doi:10.1242/dev.128.23.4757 · Cited by 89
Weiss, J. B., Suyama, K., Lee, H.-H., & Scott, M. (2001) · Cell · doi:10.1016/s0092-8674(01)00540-2 · Cited by 93
“Two-color in situ hybridizations and in situ hybridization 719–729. and antibody labeling were as in Weiss et al., 1998 and Knirr et Brand, A.H., and Perrimon, N. (1993).”
BackgroundMethodInfluentialSelf-citationEarly evolution of a homeobox gene: the parahox gene Gsx in the Cnidaria and the Bilateria
Finnerty, J. R., Paulson, D. A., Burton, P. M., Pang, K., & Martindale, M. Q. (2003) · Evolution & Development · doi:10.1046/j.1525-142x.2003.03041.x · Cited by 85
“Furthermore, in a pattern comparable with that of Drosophila, the region expressing gsh-1 is flanked by regions expressingmsh/msx and vnd/Nk-2 (Weiss et al. 1998).”
BackgroundResultInfluentialDpp and Hh signaling in theDrosophilaembryonic eye field
Chang, T., Mazotta, J., Dumstrei, K., Dumitrescu, A., & Hartenstein, V. (2001) · Development · doi:10.1242/dev.128.23.4691 · Cited by 81
Beyond the Hox: how widespread is homeobox gene clustering?
Holland, P. W. H. (2001) · Journal of Anatomy · doi:10.1046/j.1469-7580.199.parts1-2.3.x · Cited by 91
Sen, S., Chanchani, S., Southall, T. D., & Doe, C. Q. (2019) · eLife · doi:10.7554/elife.44036 · Cited by 72
“expressed in the lateral column (Figure 1A, left) (Isshiki et al., 1997; McDonald et al., 1998; Weiss et al., 1998).”
BackgroundSelf-citationGene structure and larval expression of cnox-2Am from the coral Acropora millepora
C. Hayward, D., Catmull, J., Reece-Hoyes, J. S., Berghammer, H., Dodd, H., Hann, S. J., Miller, D. J., & Ball, E. E. (2001) · Development Genes and Evolution · doi:10.1007/s004270000112 · Cited by 79
“The Drosophila Gsx ortholog, ind, is required for the specification of intermediate column neuroblasts in the developing neuroectoderm ( Weiss et al. 1998 ).”
BackgroundA two‐step process in the emergence of neurogenesis
Galliot, B., & Quiquand, M. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07829.x · Cited by 77
“…specify neuronal progenitors in the ventral telencephalon (Toresson & Campbell, 2001; Yun et al., 2003); on the other hand Gsx ⁄ Ind promotes patterning at intermediate dorsal-ventral positions along the neural tube in both vertebrates and Drosophila (Weiss et al., 1998; Cornell & Ohlen, 2000).”
BackgroundEvolution of the dorsal-ventral patterning network in the mosquito, Anopheles gambiae
Goltsev, Y., Fuse, N., Frasch, M., Zinzen, R. P., Lanzaro, G. C., & Levine, M. (2007) · Development · doi:10.1242/dev.02863 · Cited by 77
“In D. melanogaster, intermediate and low levels of the Dorsal gradient lead to sequential patterns of vnd and ind expression, which pattern the medial and lateral portions of the future nerve cord (McDonald et al., 1998; Weiss et al., 1998).”
BackgroundZhao, G., & Skeath, J. B. (2002) · Development · doi:10.1242/dev.129.5.1165 · Cited by 76
Whole-genome analysis of Drosophila gastrulation
Stathopoulos, A., & Levine, M. (2004) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2004.07.004 · Cited by 71
Evolutionary crossroads in developmental biology
Patel, N. H. (2012) · Development · doi:10.1242/dev.085464 · Cited by 77
Wang, W., Lo, P. C. H., Frasch, M., & Lufkin, T. (2000) · Mechanisms of Development · doi:10.1016/s0925-4773(00)00488-3 · Cited by 68
“Interestingly, the expression of Drosophila Hmx in three stripes within the procephalic domain is reminiscent of the combined expression of the homeobox genes vnd, ind,and msh in three stripes along the ventral neuroectoderm (D'Alessio and Frasch, 1996; Jimenez et al., 1995; Weiss et al., 1998).”
Cowden, J., & Levine, M. (2003) · Developmental Biology · doi:10.1016/s0012-1606(03)00395-6 · Cited by 68
ParaHox gene expression in the polychaete annelid Capitella sp. I
Fröbius, A. C., & Seaver, E. C. (2006) · Development Genes and Evolution · doi:10.1007/s00427-005-0049-0 · Cited by 66
“Drosophila Gsx (ind) is expressed prominently in a column of neuroblasts along the length of the ventral nerve cord and also in a subset of brain neuroblasts, including a few of the protocerebrum (Urbach and Technau 2003; Weiss et al. 1998).”
BackgroundComparative transcriptomics enlarges the toolkit of known developmental genes in mollusks
de Oliveira, A. L., Wollesen, T., Kristof, A., Scherholz, M., Redl, E., Todt, C., Bleidorn, C., & Wanninger, A. (2016) · BMC Genomics · doi:10.1186/s12864-016-3080-9 · Cited by 65
“However, loss of certain genes in both Hox and ParaHox clusters has been described as a recurrent event in the evolutionary history of metazoans [16, 88, 89] including mollusks [45, 49, 90].”
BackgroundFeatures of the ancestral bilaterian inferred from Platynereis dumerilii ParaHox genes
Hui, J. H. L., Raible, F., Korchagina, N. M., Dray, N., Samain, S., Magdelenat, G., Jubin, C., Segurens, B., Balavoine, G., Arendt, D., et al. (2009) · BMC Biology · doi:10.1186/1741-7007-7-43 · Cited by 60
“There are also domains of expression in the head region of these insects that have yet to be fully characterised, but do include expression in neural cells [11,36,37].”
BackgroundInfluentialBirkholz, O., Rickert, C., Berger, C., Urbach, R., & Technau, G. M. (2013) · Development · doi:10.1242/dev.090043 · Cited by 61
Drosophila Embryonic CNS Development: Neurogenesis, Gliogenesis, Cell Fate, and Differentiation
Crews, S. T. (2019) · Genetics · doi:10.1534/genetics.119.300974 · Cited by 57
Brody, T., Stivers, C., Nagle, J. W., et al. (2002) · Mechanisms of Development · doi:10.1016/s0925-4773(02)00010-2 · Cited by 58
Conservation of neurogenic genes and mechanisms
Chan, Y.-M., & Jan, Y. N. (1999) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(99)00017-3 · Cited by 58
Initial neurogenesis in Drosophila
Hartenstein, V., & Wodarz, A. (2013) · Wiley Interdisciplinary Reviews Developmental Biology · doi:10.1002/wdev.111 · Cited by 58
Scott, M. P. (2000) · Cell · doi:10.1016/s0092-8674(00)81681-5 · Cited by 57
“Modified from Weiss et al. (1998). form the neural tube does the flipping.”
BackgroundSelf-citationLocalized repressors delineate the neurogenic ectoderm in the early Drosophila embryo
Stathopoulos, A., & Levine, M. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2005.02.003 · Cited by 56
Gene expression patterns in primary neuronal clusters of the Drosophila embryonic brain
Sprecher, S. G., Reichert, H., & Hartenstein, V. (2007) · Gene Expression Patterns · doi:10.1016/j.modgep.2007.01.004 · Cited by 58
“…genes vnd, intermediate neuroblasts defective (ind) and msh are expressed and required in longitudinal domains that form a ventral (vnd), intermediate (ind) and dorsal (msh) column in the ventral neurectoderm (Isshiki et al., 1997; McDonald et al., 1998; Chu et al., 1998; Weiss et al., 1998).”
BackgroundKinetics of gene derepression by ERK signaling
Lim, B., Samper, N., Lu, H., Rushlow, C. A., Jiménez, G., & Shvartsman, S. Y. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303635110 · Cited by 54
Kriks, S., Lanuza, G. M., Mizuguchi, R., Nakafuku, M., & Goulding, M. (2005) · Development · doi:10.1242/dev.01878 · Cited by 52
“Gsh2 and its closely related homolog Gsh1 are expressed in progenitors in the dorsal ventricular zone (Szucsik et al., 1997; Weiss et al., 1998).”
BackgroundResultInfluentialTranscriptional mechanisms in the development of motor control
Jurata, L. W., Thomas, J. B., & Pfaff, S. L. (2000) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(99)00053-7 · Cited by 52
Cellular and molecular aspects of striatal development
Jain, M., Armstrong, R. J. E., Barker, R. A., & Rosser, A. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00555-x · Cited by 49
Combined-method phylogenetic analysis of Hox and ParaHox genes of the metazoa
Kourakis, M. J., & Martindale, M. Q. (2000) · Journal of Experimental Zoology · doi:10.1002/1097-010x(20000815)288:2 · Cited by 51
Otx genes in the development and evolution of the vertebrate brain
Boyl, P. P., Signore, M., Annino, A., Martı́nez-Barberá, J. P., Acampora, D., & Simeone, A. (2001) · International Journal of Developmental Neuroscience · doi:10.1016/s0736-5748(01)00003-x · Cited by 48
“2 ; ind/Gsh and Msh/Msx) (Arendt and Nübler-Jung, 1996; D’Alessio and Frasch, 1996; Weiss et al., 1998).”
Msx1 disruption leads to diencephalon defects and hydrocephalus
Ramos, C., Fernández‐Llebrez, P., Bach, A., Robert, B., & Soriano, E. (2004) · Developmental Dynamics · doi:10.1002/dvdy.20070 · Cited by 48
“…in vivo for the role of the msh/Msx genes in neural development and suggest that they may perform phylogenetically conserved functions in the patterning of the neuroectoderm (D’Alessio and Frasch, 1996; Isshiki et al., 1997; Maden et al., 1997; Weiss et al., 1998; Cornell and von Ohlen, 2000).”
BackgroundGenetic Regulation of Vertebrate Forebrain Development by Homeobox Genes
Leung, R. F., George, A. M., Roussel, E., Faux, M. C., Wigle, J. T., & Eisenstat, D. D. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.843794 · Cited by 40
Homeobox genes in vertebrate forebrain development and disease
Wigle, J. T., & Eisenstat, D. D. (2008) · Clinical Genetics · doi:10.1111/j.1399-0004.2008.00967.x · Cited by 50
“In the Ind mutant flies, there is a loss of intermediate neuroblasts demonstrating the essential role of Ind in their development (105).”
BackgroundIkuta, T., Chen, Y., Annunziata, R., Ting, H.-C., Tung, C., Koyanagi, R., Tagawa, K., Humphreys, T., Fujiyama, A., Saiga, H., et al. (2013) · BMC Evolutionary Biology · doi:10.1186/1471-2148-13-129 · Cited by 44
Intact cluster and chordate-like expression of ParaHox genes in a sea star
Annunziata, R., Martı́nez, P., & Arnone, M. I. (2013) · BMC Biology · doi:10.1186/1741-7007-11-68 · Cited by 46
Wheeler, S. R., Carrico, M. L., Wilson, B. A., & Skeath, J. B. (2005) · Developmental Biology · doi:10.1016/j.ydbio.2004.12.031 · Cited by 47
Ferrier, D. E. K., & Holland, P. W. H. (2001) · Evolution & Development · doi:10.1046/j.1525-142x.2001.003004263.x · Cited by 46
“Where genomic structure is known, Gsx genes either have no intron ( D. melanogaster ) (Weiss et al. 1998) or a short intron (479 bp in mouse Gsx1 ) (Li et al. 1996) between these two motifs.”
BackgroundInfluentialSprecher, S. G., & Reichert, H. (2003) · Arthropod Structure & Development · doi:10.1016/s1467-8039(03)00007-0 · Cited by 42
Arendt, D. (2005) · Theory in Biosciences · doi:10.1007/bf02814483 · Cited by 50
“2, ind, and msx genes in longitudinal columns in the neuroectoderm is best explained by evolutionary conservation (Arendt and Ntibler-Jung, 1999; D'Alessio and Frasch, 1996; Weiss et al., 1998).”
BackgroundCole, A. G., Rizzo, F. M., Martı́nez, P., Fernandez-Serra, M., & Arnone, M. I. (2009) · Development · doi:10.1242/dev.029959 · Cited by 44
Kulakova, M. A., Cook, C. E., & Andreeva, T. F. (2008) · BMC Developmental Biology · doi:10.1186/1471-213x-8-61 · Cited by 44
“However the full set of ParaHox genes has not yet been found in any ecdysozoan taxon, including two taxa for which complete genomes are available: the fruit fly Drosophila melanogaster has no Xlox ortholog [26,27] while the nematode Caenorhabitis elegans has neither Gsh nor Xlox orthologs [28].”
Metadata
- Authors
- Weiss, J. B., Von Ohlen, T., Mellerick, D. M., Dressler, G., Doe, C. Q., & Scott, M. P.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1998-11-15
- Volume
- 12
- Issue
- 22
- Pages
- 3591-3602
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC317240
- OpenAlex
- W7073826300
- Semantic Scholar
- d5b2bd0f775838548cd175b48517cdd9cce81c8a
- Cited by
- 236
- References
- 57
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 14 · 2023: 1 · 2022: 7 · 2021: 2 · 2020: 2 · 2019: 7 · 2018: 1 · 2017: 5 · 2016: 8 · 2015: 10 · 2014: 1 · 2013: 8 · 2012: 4
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Howard Hughes Medical Institute
- National Institutes of Health
- National Heart, Lung, and Blood Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- dorsoventral patterning, Drosophila central nervous system, homeobox genes, negative regulation, evolutionary conservation
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Central Nervous System, Drosophila, Genes, Homeobox, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Repressor Proteins, RNA, Messenger, Transcription Factors, Trans-Activators, Sequence Alignment, Genes, Insect, In Situ Hybridization, Sequence Analysis, DNA, Homeodomain Proteins, Gene Expression Regulation, Developmental, DNA Footprinting, Body Patterning, Drosophila Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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