CoChat
Sign Up
Cited by 376MicroRNA in disease regulationDevelopmental Biology and Gene RegulationNeurogenesis and neuroplasticity mechanisms

MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system

Open access
Kapsimali, Marika, Kloosterman, Wigard P, de Bruijn, Ewart, Rosa, Frederic, Plasterk, Ronald HA, Wilson, Stephen W·2007·Genome Biology
DOI 10.1186/gb-2007-8-8-r173PMC PMC2375003
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: MicroRNA (miRNA) encoding genes are abundant in vertebrate genomes but very few have been studied in any detail. Bioinformatic tools allow prediction of miRNA targets and this information coupled with knowledge of miRNA expression profiles facilitates formulation of hypotheses of miRNA function. Although the central nervous system (CNS) is a prominent site of miRNA expression, virtually nothing is known about the spatial and temporal expression profiles of miRNAs in the brain. To provide an overview of the breadth of miRNA expression in the CNS, we performed a comprehensive analysis of the neuroanatomical expression profiles of 38 abundant conserved miRNAs in developing and adult zebrafish brain. Results: Our results show miRNAs have a wide variety of different expression profiles in neural cells, including: expression in neuronal precursors and stem cells (for example, miR-92b ); expression associated with transition from proliferation to differentiation (for example, miR-124 ); constitutive expression in mature neurons ( miR-124 again); expression in both proliferative cells and their differentiated progeny (for example, miR-9 ); regionally restricted expression (for example, miR-222 in telencephalon); and cell-type specific expression (for example, miR-218a in motor neurons). Conclusion: The data we present facilitate prediction of likely modes of miRNA function in the CNS and many miRNA expression profiles are consistent with the mutual exclusion mode of function in which there is spatial or temporal exclusion of miRNAs and their targets. However, some miRNAs, such as those with cell-type specific expression, are more likely to be co-expressed with their targets. Our data provide an important resource for future functional studies of miRNAs in the CNS.

AI snapshot

Written from the paper’s full text.

TL;DR

This study used LNA in situ hybridization to profile 38 conserved vertebrate miRNAs in zebrafish neural tissue from larval stages through adulthood, revealing wide diversity in spatial and temporal expression. It classifies miRNA expression into proliferating-cell, differentiating-cell, broadly neural, region/nucleus-specific, cell-type-specific, conserved, and stage-changing patterns.

Key findings

  • Surveyed 38 conserved miRNAs at 3 and/or 5 days post-fertilization and/or 6 weeks and/or adult zebrafish; expression ranged from single cell types to the majority of CNS cells and from transient to constitutive.
  • Examples include miR-92b in proliferative zones, miR-124 in virtually all differentiating cells, miR-9 in both proliferating and differentiating cells, miR-137 and miR-222 in restricted brain regions/nuclei, miR-218a in cranial and spinal motor neurons, miR-183/miR-182/miR-96 in sensory cells, and miR-375 in pituitary and scattered hypothalamic cells.
  • Many profiles were conserved between larval and adult stages (e.g., miR-92b, miR-124, miR-9, miR-137, miR-222), while others changed (e.g., miR-219 lost from larval thalamus but gained in adult tract-associated cells; miR-34 and miR-218a expanded rostrally in adults).
  • Family/cluster members showed subtle differences (miR-181a vs miR-181b; miR-221 vs miR-222), and probes with two mismatches eliminated specific signal, supporting discrimination of closely related miRNAs.

Methods

  • In situ hybridization with locked nucleic acid (LNA) probes against 38 miRNAs in zebrafish at 3 and/or 5 dpf and/or 6 weeks young adult and/or adult; adult brains were dissected, fixed, sectioned at 7 μm, and counterstained.
  • Combined whole-mount in situ hybridization with anti-GFP immunostaining in Tg(huc:gfp) or Tg(isl1:gfp) embryos, plus confocal microscopy; brain areas annotated using zebrafish embryonic and adult atlases.
  • Descriptive neuroanatomical expression profiling; miRNA target predictions used miRBase and Zebrafish microRNA Targets resources.

Limitations

  • Stated: one-mismatch LNA probes for let-7a, miR-92b, and miR-153a strongly reduced but did not eliminate signal, so cross-hybridization with other family members cannot be excluded; two mismatches in the miR-181a probe eliminated specific signal.
  • Stated: in some adult brain preparations deep tissue did not label well, so absence of expression should be interpreted cautiously; larval neuroanatomical annotation is not always definitive.
  • Stated: the authors cannot formally prove expression is in the same cells over time. Evident from the text: the study is descriptive expression profiling and does not functionally test miRNA roles or validate targets.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1186/gb-2007-8-8-r173

Cites

69 of 69 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 40 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Outside the CNS, miR-183 is expressed in cells that include peripheral sensory neuromasts, olfactory sensory neurons and hair cells of the ear.

    “Outside of the CNS, miR-183 is expressed in cells that include peripheral sensory neuromasts, olfactory sensory neurons and hair cells of the ear (Additional data file 15, and Table E in Additional data file 27).”
    Quote in the paperNot a substantial claim
  • Findingown data

    miR-222 shows conserved restricted expression in the rostral brain throughout life with domains in the telencephalon, hypothalamus and posterior tubercular area.

    “Like miR-137, miR-222 shows conserved restricted expression in the rostral brain throughout life with domains in the telencephalon (for instance, compare P in Figure 3h with P, Dm, Dd, Dl, and Dc in Figure 3i,j), hypothalamus (DIL, TLa, lr/Hd-lr in Figure 3k,l) and posterior tubercular area (PTv in Figure 3k and nPVO in Figure 3l; see also Additional data file 20, and Tables D and I in Additional”
    Quote in the paperNot a substantial claim
  • Findingown data

    miR-138 shows a widespread but more restricted pattern of expression than miR-124 in the larval brain.

    “whereas miR-138 (Additional data file 11, and Table B in Additional data file 27) shows a widespread but more restricted pattern of expression.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Both miR-181a and miR-181b are expressed in cells associated with the visual system, including retinal amacrine cells and ganglion cells.

    “We observe that both are expressed in cells associated with the visual system, including retinal amacrine cells (INL) and ganglion cells (GCL in Figure 2h; Additional data files 13 and 14).”
    Quote in the paperNot a substantial claim
  • Findingown data

    let-7a and let-7c appear to lack the retinal CMZ expression seen for let-7b.

    “let-7a and let-7c, which differ in their sequence from let-7b by two and one nucleotide, respectively, located outside the seed region, appear to lack this retinal expression, although we cannot exclude that these LNA probes cross-hybridize to various let-7 family members in different brain areas (Additional data files 22-24 and 27-29).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 42
  • Classified as probably not a substantial claim. 26

  • May combine two claims.

    Findingown data

    miR-34 expression is absent from forebrain and midbrain and present only in the caudal ventral and lateral isthmus and hindbrain, including ventral and lateral medulla oblongata cells, presumptive octaval area and reticular formation cells.

    “In contrast, miR-34 expression is absent from forebrain and midbrain and present only in the caudal ventral and lateral isthmus and hindbrain, including ventral and lateral medulla oblongata cells (MO in Figure 5c), presumptive octaval area (OA in Figure 5c), reticular formation cells (intermediate reticular formation-(IMRF) and Mauthner cell (MAC) in Figure 5c; Additional data file 5, and Table D”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    miR-182 and miR-96 show almost identical expression patterns to miR-183, although expression is not as robust.

    “miR-182 and miR-96 show almost identical expression patterns to miR-183 (Figure 2f,g; and Table E in Additional data file 27), although expression is not as robust.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The expression pattern of miR-181a and miR-181b is highly reminiscent of expression of the huC gene, which encodes an RNA binding protein expressed in nearly all CNS neurons but the same subsets of retinal cells as miR-181a and miR-181b.

    “This pattern is highly reminiscent of expression of the huC gene (Figure 2i), which encodes an RNA binding protein expressed in nearly all CNS neurons but the same subsets of retinal cells as miR-181a and miR-181b.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    let-7b expression is restricted to the ciliary marginal zone (CMZ) of the retina, with expression absent from all mature retinal neurons.

    “Like miR-92b, let-7b expression is restricted to the CMZ of the retina, with expression absent from all mature retinal neurons (arrow in Figure 2b); let-7b has broader expression elsewhere in the larval brain (Additional data file 23).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The expression of miR-183, miR-182 and miR-96 in peripheral sensory neural cells overlaps with miR-200a, although miR-200a lacks the CNS and cranial ganglia expression sites common to miR-183, miR-182 and miR-96.

    “The expression of these miRNAs in peripheral sensory neural cells overlaps with miR-200a (Additional data file 16), although miR-200a lacks the CNS and cranial ganglia expression sites common to miR-183, miR-182 and miR-96 (Table E in Additional data file 27).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    miR-9 expression is not ubiquitous in neural cells; the epithalamus and hypothalamic lateral torus are devoid of expression.

    “Expression is not ubiquitous in neural cells as some areas such as the epithalamus and hypothalamic lateral torus are devoid of expression (Additional data files 2 and 3, and Table A in Additional data file 27).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Both miR-181a and miR-181b are also expressed in migrated pretectal and tectal cells and more weakly in many differentiating cells throughout the brain, with some stronger sites of expression in central pallium and medulla oblongata.

    “Both miRNAs are also expressed in migrated pretectal (M1 in Figure 4a,b) and tectal cells (TeO in Figure 4a,b) and more weakly in many differentiating cells throughout the brain, with some stronger sites of expression in central pallium and medulla oblongata (Additional data files 13 and 14, and Table C in Additional data file 27).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    miR-124 expression is excluded from periventricular cells and is detected in most differentiated cells throughout the adult brain as in the larval brain.

    “Similarly showing conserved expression over time, miR-124 expression is excluded from periventricular cells and is detected in most differentiated cells throughout the adult brain as in the larval brain (compare Vd in Figure 1h and Sd in Figure 1b; Additional data file 7, and Tables B and G in Additional data file 27).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    miR-222 and miR-221 share largely similar expression in the adult hypothalamus, but only miR-222 is expressed in the ventral intermediate hypothalamus at the larval stage.

    “For instance, miR-222 and miR-221 share largely similar expression in the adult hypothalamus (ATN, LH, Hd in Figure G of Additional data file 20 and Figure O of Additional data file 19) but only miR-222 is expressed in the ventral intermediate hypothalamus at the larval stage (Figure D of Additional data file 20 and Figure B of Additional data file 19; see also Table K in Additional data file 28”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Within the retina, miR-9 is expressed in maturing cells of the CMZ but expression is maintained only in amacrine cells of the inner nuclear layer.

    “Additionally, within the retina miR-9 is expressed in maturing cells of the CMZ (which are likely to still be proliferative) but expression is maintained only in amacrine cells of the inner nuclear layer (INL in Figure 2d).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    miR-181a and miR-181b show similar expression in the larval brain, and this is largely conserved to adult stages, although there is down-regulation in some areas such as thalamus and tegmentum.

    “miR-181a and miR-181b show similar expression in the larval brain, and this is largely conserved to adult stages (although there is down-regulation in some areas such as thalamus and tegmentum; Additional data files 13 and 14, and Tables C and H in Additional data file 27).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    miR-183 is expressed in retinal photoreceptors and weakly in some inner nuclear layer cells, pineal cells that are likely photoreceptors and perhaps also in parapineal photoreceptors.

    “miR-183 is expressed in retinal photoreceptors and weakly in some inner nuclear layer cells, pineal cells that are again likely to be photoreceptors (Figure 2e) and perhaps also in parapineal photoreceptors (Figure C in Additional data file 15).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Some of the miRNA expression patterns helped us annotate larval fish brain nuclei.

    “Some of the miRNA expression patterns helped us annotate larval fish brain nuclei.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Larval ventral thalamus expresses miR-219 but the corresponding adult thalamic nuclei do not.

    “For example, larval ventral thalamus (VT in Figure 5a) expresses miR-219 but the corresponding adult thalamic nuclei do not (ventrolateral (VL) and ventromedial (VM) in Figure 5b).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In adults, miR-219 is expressed in cells, possibly glia, associated with major tracts such as the lateral olfactory tract, post-optic commissure/optic chiasma and tract, whereas the equivalent pathways in larvae are devoid of staining.

    “Conversely, in adults, miR-219 is expressed in cells, possibly glia, associated with major tracts such as the lateral olfactory tract, post-optic commissure/optic chiasma and tract (poc and OT, respectively, in Figure 5b) whereas the equivalent pathways in larvae are devoid of staining (Figure 5a).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    miR-92b is downregulated in most mature neurons whereas miR-124 is absent from proliferative cells and widely expressed in differentiated neurons.

    “For instance, miR-92b is downregulated in most mature neurons whereas, conversely, miR-124 is absent from proliferative cells and widely expressed in differentiated neurons.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    miR-34 shows conserved expression in the larval and adult hindbrain but also expands to include forebrain and midbrain cells of the habenulae, posterior tuberculum, pretectum, optic tectum as well as novel areas of the dorsal hindbrain.

    “For instance, miR-34 shows conserved expression in the larval and adult hindbrain (Mauthner neuron, (MAC) and presumptive octavolateral area (OA) in Figure 5c; MAC and octavolateral nuclei (medial octavolateral (MON), anterior octaval (AON), magnocellular octaval (MaON) in Figure 5d) but also expands to include forebrain and midbrain cells of the habenulae (Had in Figure 5f), posterior tuberculum”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There are sharp transitions between domains of expression and non-expression, with some structures, such as the habenular nuclei, devoid of expression.

    “However, there are sharp transitions between domains of expression and non-expression, with some structures, such as the habenular nuclei, devoid of expression.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    miR-100 shows robust habenular expression while miR-92b and miR-34b are expressed in ventricular cells adjacent to the mature habenular nuclei.

    “miR-100 also shows robust habenular expression (Figure K in Additional data file 25) while miR-92b and miR-34b are expressed in ventricular cells adjacent to the mature habenular nuclei (Figure J in Additional data file 6, and Figure L in Additional data file 25).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    It reveals a wide diversity in miRNA expression, ranging from single cell types to the majority of CNS cells and from transient to constitutive expression.

    “It reveals a wide diversity in miRNA expression, ranging from single cell types to the majority of CNS cells and from transient to constitutive expression.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    A few of the miRNAs we examined show expression restricted to very few cells and usually expressing cells share some characteristics of function and/or form.

    “A few of the miRNAs we examined show expression restricted to very few cells and usually expressing cells share some characteristics of function and/or form.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    miR-222 expression is largely conserved between larvae and adults but de novo expression in the adult facial and vagal lobes is also observed.

    “As described above, miR-222 expression is also largely conserved between larvae and adults (Figure 3h-l) but de novo expression in the adult facial and vagal lobes is also observed (LVII, LX, Figure I in Additional data file 20).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    For let-7a, miR-92b and miR-153a, one internal mismatch strongly reduces the hybridization signal, but some cross-hybridization with other members of the respective miRNA families cannot be excluded.

    “We observe that in the case of let-7a, miR-92b and miR-153a, one mismatch strongly reduces the hybridization signal. Since there is still some staining left, we cannot exclude some cross-hybridization with other members of the respective miRNA families.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Mouse miR-375 is expressed in pancreatic beta cells and appears to function in the regulation of insulin secretion.

    “Although expression of mouse miR-375 in the pituitary has not been ascertained, it is expressed in pancreatic beta cells [45] and appears to function in the regulation of insulin secretion.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, Pfeffer S, Tuschl T, Rajewsky N, Rorsman P, et al: A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 2004, 432: 226-230. 10.1038/nature03076. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    There is a precedent for post-transcriptional regulation of miRNA expression, although this has not been demonstrated for different miRNAs from the same transcript.

    “There is a precedent for post-transcriptional regulation of miRNA expression [48,49], although this has not been demonstrated for different miRNAs from the same transcript.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [48] Obernosterer G, Leuschner PJ, Alenius M, Martinez J: Post-transcriptional regulation of microRNA expression. Rna. 2006, 12: 1161-1167. 10.1261/rna.2322506. source
    • cites [49] Thomson JM, Newman M, Parker JS, Morin-Kensicki EM, Wright T, Hammond SM: Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev. 2006, 20: 2202-2207. 10.1101/gad.1444406. source

  • May combine two claims.

    Interpretationown data

    Other miRNAs belonging to a particular cluster seem to largely share expression patterns but also have subtle differences in transcript localization.

    “In a similar manner, other miRNAs belonging to a particular cluster seem to largely share expression patterns but also have subtle differences in transcript localization.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    miR-181a and miR-181b differ in three nucleotides outside the seed region, suggesting that LNA probes can discriminate between their transcript expression profiles.

    “miR-181a and miR-181b belong to the same family but differ in three nucleotides outside the seed region, suggesting that LNA probes can discriminate between their transcript expression profiles (Tables K and L in Additional data file 28, and Additional data file 29).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Proliferation and production of neurons continues into adulthood in the CNS of zebrafish.

    “These observations are consistent with the fact that proliferation and production of neurons continues into adulthood in the CNS of zebrafish [46,47].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [46] Adolf B, Chapouton P, Lam CS, Topp S, Tannhauser B, Strahle U, Gotz M, Bally-Cuif L: Conserved and acquired features of adult neurogenesis in the zebrafish telencephalon. Dev Biol. 2006, 295: 278-293. 10.1016/j.ydbio.2006.03.023. source
    • cites [47] Grandel H, Kaslin J, Ganz J, Wenzel I, Brand M: Neural stem cells and neurogenesis in the adult zebrafish brain: origin, proliferation dynamics, migration and cell fate. Dev Biol. 2006, 295: 263-277. 10.1016/j.ydbio.2006.03.040. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Many of the genes in intraflagellar transport pathways are implicated in human diseases.

    “Many of the genes in these pathways are implicated in human diseases [43].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Banizs B, Pike MM, Millican CL, Ferguson WB, Komlosi P, Sheetz J, Bell PD, Schwiebert EM, Yoder BK: Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus. Development. 2005, 132: 5329-5339. 10.1242/dev.02153. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The difference in expression of miR-181a and miR-181b may be due to genomic duplication of the miRNAs.

    “This difference in expression may again be due to genomic duplication of the miRNAs.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A cluster on chromosome 8 contains both miR-181a and miR-181b, but there is an additional copy of miR-181a on chromosome 22 and of miR-181b on chromosome 20.

    “A cluster on chromosome 8 contains both miR-181a and miR-181b but there is an additional copy of miR-181a on chromosome 22 and of miR-181b on chromosome 20 [19,44].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] Ason B, Darnell DK, Wittbrodt B, Berezikov E, Kloosterman WP, Wittbrodt J, Antin PB, Plasterk RH: Differences in vertebrate microRNA expression. Proc Natl Acad Sci USA. 2006, 103: 14385-14389. 10.1073/pnas.0603529103. source

      Not checked in the free run.

    • cites [44] Griffiths-Jones S: miRBase: the microRNA sequence database. Methods Mol Biol. 2006, 342: 129-138.

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    It is not obvious why there should be differences in miR-222 and miR-221 expression as they are present in the same cluster and one would predict that they are co-transcribed.

    “It is not obvious why there should be differences in miR-222 and miR-221 expression as they are present in the same cluster and one would predict that they are co-transcribed.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    miR-137 is expressed in the adult midbrain DTN, and the cells in the larval tegmentum correspond to the presumptive midbrain DTN.

    “miR-137 is expressed in the adult midbrain DTN (Figure 3g) and given the good correspondence of localized tegmental expression between 5 dpf and adult brains, we suggest that the cells in the larval tegmentum correspond to the presumptive midbrain DTN (Figure 3e,g; for other nuclei, see Additional data file 10, and Tables C and H in Additional data file 27).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    miRNA expression is frequently region or nucleus specific and can vary in the levels of expression from one group of cells to another.

    “Together these results show that miRNA expression is frequently region or nucleus specific and can vary in the levels of expression from one group of cells to another.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The acetylation step in the in situ hybridization was often omitted since it did not change or improve signal.

    “The acetylation step in the in situ hybridization was often omitted since it did not change or improve signal.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Localized translation from mRNAs is mediated in part by mRNA binding proteins that promote translation.

    “Localized translation from mRNAs is mediated in part by mRNA binding proteins that promote translation [59,60] and a counterpart to this could be that miRNAs clear mRNAs at sites where protein activity should be low.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [59] Adler CE, Fetter RD, Bargmann CI: UNC-6/Netrin induces neuronal asymmetry and defines the site of axon formation. Nat Neurosci. 2006, 9: 511-518. 10.1038/nn1666. source
    • cites [60] Leung KM, van Horck FP, Lin AC, Allison R, Standart N, Holt CE: Asymmetrical beta-actin mRNA translation in growth cones mediates attractive turning to netrin-1. Nat Neurosci. 2006, 9: 1247-1256. 10.1038/nn1775. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    As the silencing of loci is generally efficient, one might conclude that for most of the time in most mature neurons, some miRNAs are doing very little indeed, consistent with the idea that miRNAs confer robustness to programs of gene expression.

    “As the silencing of loci is generally efficient, one might conclude that for most of the time in most mature neurons, some miRNAs are doing very little indeed, consistent with the idea that miRNAs confer robustness to programs of gene expression [11,12].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [11] Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, Burge CB, Bartel DP: The widespread impact of mammalian microRNAs on mRNA repression and evolution. Science. 2005, 310: 1817-1821. 10.1126/science.1121158. source
    • cites [12] Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM: Animal microRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution. Cell. 2005, 123: 1133-1146. 10.1016/j.cell.2005.11.023. source
    • Rests on an assumption: The silencing of loci is generally efficient.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    There are well-described mechanisms for repressing and silencing loci.

    “There are well-described mechanisms for repressing and silencing loci (for example, [54]), but the absolute efficacy of such mechanisms is unknown.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Talbert PB, Henikoff S: Spreading of silent chromatin: inaction at a distance. Nat Rev Genet. 2006, 7: 793-803. 10.1038/nrg1920. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Mismatch LNA probe sequences were used to test specificity of corresponding fully matching LNA probes.

    “Additional data file 28 includes Tables J-L, listing the miRNAs analyzed, the family/cluster they belong to and the mismatch LNA probe sequences used to test specificity of corresponding fully matching LNA probes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    miRNAs that are induced when cells transition from one state to another are likely to target mRNAs that are expressed during the initial state and not required during the second state.

    “miRNAs that are induced when cells transition from one state to another are likely to target mRNAs that are expressed during the initial state and not required during the second state.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The differences in miR-219 expression between larva and adult brain suggest downregulation of expression in most cells in the adult brain and either conserved or de novo expression in a few discrete cell populations.

    “These differences between larva and adult brain suggest downregulation of expression in most cells in the adult brain and either conserved or de novo expression in a few discrete cell populations (Additional data file 18, Tables B and G in Additional data file 27).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Penetration of all reagents even in adult brains was generally very good, although in some preparations deep tissue in the brain did not label well and readers should be cautious about interpretation regarding absence of expression in such cases.

    “Penetration of all reagents even in adult brains was generally very good, although in some preparations deep tissue in the brain did not label well and readers should be cautious about interpretation regarding absence of expression in such cases.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Some mRNAs are localized and translated locally within neurons.

    “Given that some mRNAs are localized and translated locally within neurons (for example, [57,58]), an attractive possibility is that cell-type specific brain miRNAs regulate spatially localized translation of proteins.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [57] Raab-Graham KF, Haddick PC, Jan YN, Jan LY: Activity- and mTOR-dependent suppression of Kv1.1 channel mRNA translation in dendrites. Science. 2006, 314: 144-148. 10.1126/science.1131693. source
    • cites [58] Piper M, Holt C: RNA translation in axons. Annu Rev Cell Dev Biol. 2004, 20: 505-523. 10.1146/annurev.cellbio.20.010403.111746. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    miR-134 transcripts are localized to the dendritic compartments in which they function and miRNA activity is spatially/temporally regulated by extracellular signals.

    “For instance, miR-134 transcripts are localized to the dendritic compartments in which they function and miRNA activity is spatially/temporally regulated by extracellular signals [29].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M, Greenberg ME: A brain-specific microRNA regulates dendritic spine development. Nature. 2006, 439: 283-289. 10.1038/nature04367. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The mutual exclusion of miRNAs and their targets may be in either space or in time.

    “The mutual exclusion of miRNAs and their targets may be in either space or in time.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A common feature of miRNA function is mutually exclusive expression of miRNAs and their target mRNAs.

    “A common feature of miRNA function is one of mutually exclusive expression of miRNAs and their target mRNAs [11,12].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [11] Farh KK, Grimson A, Jan C, Lewis BP, Johnston WK, Lim LP, Burge CB, Bartel DP: The widespread impact of mammalian microRNAs on mRNA repression and evolution. Science. 2005, 310: 1817-1821. 10.1126/science.1121158. source
    • cites [12] Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM: Animal microRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution. Cell. 2005, 123: 1133-1146. 10.1016/j.cell.2005.11.023. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Recent studies suggest that there is a huge variability in the level of transcription at equivalent active loci in different cells.

    “Certainly, recent studies suggest that there is a huge variability in the level of transcription at equivalent active loci in different cells [55] and perhaps there is comparable variability at repressed loci.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] Raj A, Peskin CS, Tranchina D, Vargas DY, Tyagi S: Stochastic mRNA synthesis in mammalian cells. PLoS Biol. 2006, 4: e309-10.1371/journal.pbio.0040309. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In zebrafish, miR-430 targets a large number of maternally deposited transcripts at the onset of zygotic transcription.

    “For instance, in zebrafish, miR-430 targets a large number of maternally deposited transcripts at the onset of zygotic transcription [6] and many examples of spatially exclusive expression domains of miRNAs and their targets have been documented (for example, [12,53]).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Giraldez AJ, Mishima Y, Rihel J, Grocock RJ, Van Dongen S, Inoue K, Enright AJ, Schier AF: Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science. 2006, 312: 75-79. 10.1126/science.1122689. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The translation of beta-actin in neuronal processes is regulated by Vg1RBP, a protein that binds the 3' UTR of mRNAs.

    “It is intriguing that the translation of beta-actin in neuronal processes is regulated by Vg1RBP, a protein that binds the 3' UTR of mRNAs [60] and may, therefore, shield the mRNA from miRNAs.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Leung KM, van Horck FP, Lin AC, Allison R, Standart N, Holt CE: Asymmetrical beta-actin mRNA translation in growth cones mediates attractive turning to netrin-1. Nat Neurosci. 2006, 9: 1247-1256. 10.1038/nn1775. source

  • May combine two claims.

    Premisecitation

    mRNAs from genes required for general cellular machinery are protected from miRNA action through possession of short 3' UTRs that are poor miRNA targets and genes required for specific cellular functions of the specific cell type are often miRNA anti-targets - that is, their 3' UTRs lack sequences that would enable binding of co-expressed miRNAs.

    “mRNAs from genes required for general cellular machinery are protected from miRNA action through possession of short 3' UTRs that are poor miRNA targets and genes required for specific cellular functions of the specific cell type are often miRNA anti-targets - that is, their 3' UTRs lack sequences that would enable binding of co-expressed miRNAs [12].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12] Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM: Animal microRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution. Cell. 2005, 123: 1133-1146. 10.1016/j.cell.2005.11.023. source

  • May combine two claims.

    Interpretationown data

    The first is to function in neural stem cells/progenitors and the second is to facilitate the clearance of target mRNAs at spatial or temporal transitions.

    “The first is to function in neural stem cells/progenitors and the second is to facilitate the clearance of target mRNAs at spatial or temporal transitions.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    miR-134 is localized to dendrites and appears to modulate the levels of activity of a kinase that influences dendrite morphogenesis.

    “However, miR-134 is localized to dendrites and appears to modulate the levels of activity of a kinase that influences dendrite morphogenesis [29].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M, Greenberg ME: A brain-specific microRNA regulates dendritic spine development. Nature. 2006, 439: 283-289. 10.1038/nature04367. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Major changes in the transcriptome that occur when cells transition between states are thought to be brought about by transcriptional mechanisms independent of miRNA function and so it seems likely that many target mRNAs will not be actively transcribed once a transition has occurred.

    “Major changes in the transcriptome that occur when cells transition between states are thought to be brought about by transcriptional mechanisms independent of miRNA function and so it seems likely that many target mRNAs will not be actively transcribed once a transition has occurred (for example, [6]).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Giraldez AJ, Mishima Y, Rihel J, Grocock RJ, Van Dongen S, Inoue K, Enright AJ, Schier AF: Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science. 2006, 312: 75-79. 10.1126/science.1122689. source

  • May combine two claims.

    Interpretationown data

    Specific brain nuclei can express combinations of different miRNAs, some throughout life and some associated with differentiation.

    “This analysis of habenular miRNA profiles illustrates that specific brain nuclei can express combinations of different miRNAs, some throughout life and some associated with differentiation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    This profile is one of the best conserved miRNA patterns, as a similar restriction to mature neurons is seen for mouse and fly miR-124.

    “This profile is one of the best conserved miRNA patterns, as a similar restriction to mature neurons is seen for mouse and fly miR-124 [12,30].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [12] Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM: Animal microRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution. Cell. 2005, 123: 1133-1146. 10.1016/j.cell.2005.11.023. source
    • cites [30] Smirnova L, Grafe A, Seiler A, Schumacher S, Nitsch R, Wulczyn FG: Regulation of miRNA expression during neural cell specification. Eur J Neurosci. 2005, 21: 1469-1477. source

  • May combine two claims.

    Interpretationcitation

    In situations of mutually exclusive expression, the miRNA is expressed at high levels in comparison to the target mRNA and the expectation is that miRNA function is to maintain low levels of target gene activity.

    “In such situations, the miRNA is expressed at high levels in comparison to the target mRNA and the expectation is that miRNA function is to maintain low levels of target gene activity.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    mRNAs can be protected from miRNA attack as seen, for instance, in germ cells.

    “mRNAs can be protected from miRNA attack as seen, for instance, in germ cells [7], although we are unaware of examples of such regulation occurring within different cellular compartments.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Mishima Y, Giraldez AJ, Takeda Y, Fujiwara T, Sakamoto H, Schier AF, Inoue K: Differential regulation of germline mRNAs in soma and germ cells by zebrafish miR-430. Curr Biol. 2006, 16: 2135-2142. 10.1016/j.cub.2006.08.086. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Many examples of spatially exclusive expression domains of miRNAs and their targets have been documented.

    “For instance, in zebrafish, miR-430 targets a large number of maternally deposited transcripts at the onset of zygotic transcription [6] and many examples of spatially exclusive expression domains of miRNAs and their targets have been documented (for example, [12,53]).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [12] Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM: Animal microRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution. Cell. 2005, 123: 1133-1146. 10.1016/j.cell.2005.11.023. source
    • cites [53] Li Y, Wang F, Lee JA, Gao FB: MicroRNA-9a ensures the precise specification of sensory organ precursors in Drosophila. Genes Dev. 2006, 20: 2793-2805. 10.1101/gad.1466306. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Neuroanatomical documentation of the zebrafish brain, particularly at larval stages, is far from complete and so our annotation is not always definitive.

    “Neuroanatomical documentation of the zebrafish brain, particularly at larval stages, is far from complete and so our annotation is not always definitive.”
    Quote in the paperNot a substantial claim
59 of 59

  • The paper relies on this without support.

    Expression profiles of miRNAs allow generalized predictions regarding miRNA roles.

    “Although one cannot make specific conclusions regarding function based upon expression pattern alone, expression profiles do allow one to make generalized predictions regarding miRNA roles.”

  • The paper relies on this without support.

    The 38 selected miRNAs are representative of conserved vertebrate miRNAs in the CNS.

    “Based on our previous miRNA expression analyses [18,24], we selected 38 conserved vertebrate miRNAs from different families and with distinct expression profiles in the CNS and studied their expression in zebrafish neural tissue from development into adulthood.”

  • The paper relies on this without support.

    In situ hybridization signal with LNA probes reliably reports the expression of the targeted miRNA.

    “In order to survey the expression patterns of miRNAs in the brain, we performed in situ hybridizations with locked nucleic acid (LNA) probes to 38 different miRNAs (Table J in Additional data file 28,) at 3 and/or 5 days and/or 6 weeks (young adult ('Y-Ad' in Additional data files 1-29)) and/or adult zebrafish (adult ('A' in Additional data files 1-29)).”

  • The paper relies on this without support.

    The silencing of loci is generally efficient.

    “As the silencing of loci is generally efficient”

  • The paper relies on this without support.

    Other protein coding genes not required by the cell are transcriptionally silenced.

    “Other protein coding genes not required by the cell are transcriptionally silenced”

  • The paper relies on this without support.

    In some instances, miRNAs are expressed in the same cells at the same time as their target genes.

    “in some instances, miRNAs are expressed in the same cells at the same time as their target genes”

  • The paper relies on this without support.

    There is a great deal of regulation of protein activity levels within cells but there are not many examples of miRNAs involved in such regulation.

    “There is a great deal of regulation of protein activity levels within cells but there are not many examples of miRNAs involved in such regulation.”

  • The paper relies on this without support.

    Each neural cell requires the expression and function of a certain proportion of all possible protein coding genes.

    “each neural cell requires the expression and function of a certain proportion of all possible protein coding genes”

  • The paper relies on this without support.

    The mutual exclusion model of miRNA function may underlie most functions of animal miRNAs.

    “The mutual exclusion model of miRNA function may underlie most functions of animal miRNAs”
9 of 9

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Kapsimali, M., Kloosterman, W. P., de Bruijn, E., Rosa, F., Plasterk, R. H., & Wilson, S. W.
Affiliations
University College London (GB)
Corresponding author
  • Plasterk, Ronald HA
  • Wilson, Stephen W
ORCID
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2007-08-21
Volume
8
Issue
8
Pages
R173-R173
ISSN
  • 1465-6906 (ISSN-L)
  • 1474-760X
DOI
10.1186/gb-2007-8-8-r173
PMC
PMC2375003
OpenAlex
W2096304780
Semantic Scholar
c50acd2cdddea4ee8afdc71bad1ab41d1a25196d
Cited by
376
References
69
Citations by year
2026: 3 · 2025: 4 · 2024: 7 · 2023: 11 · 2022: 10 · 2021: 16 · 2020: 17 · 2019: 10 · 2018: 22 · 2017: 16 · 2016: 21 · 2015: 22 · 2014: 31 · 2013: 36 · 2012: 37
FWCI
9.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Wellcome Trust
  • Institut National de la Santé et de la Recherche Médicale
  • ZonMw
  • Centre National de la Recherche Scientifique
  • Biotechnology and Biological Sciences Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
microRNA, central nervous system development, zebrafish brain, microRNA expression profiles, cell type-specific gene expression, neuronal precursors, neural stem cells, neuronal differentiation, motor neurons, telencephalon, miR-124, miR-9, miR-222, miR-92b, spatiotemporal gene expression
MeSH terms
Animals, Brain, Cell Differentiation, Larva, Zebrafish, Gene Expression Regulation, Developmental, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, MicroRNAs, Organogenesis

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-11-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-06.

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 ›

Are you an author, or do you see a problem with this page? Request a review