Cited by 23Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationNeuroinflammation and Neurodegeneration Mechanisms

The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index; 3 of the 47 sources its claims cite were checked for support.

Dynamic expression of Dab2 in the mouse embryonic central nervous system

Open access
Cheung, Kwok-Kuen, Mok, Samuel C, Rezaie, Payam, Chan, Wood Yee·2008·BMC Developmental Biology

Abstract

Background: Dab2, one of two mammalian orthologs of Drosophila Disabled, has been shown to be involved in cell positioning and formation of visceral endoderm during mouse embryogenesis, but its role in neuronal development is not yet fully understood. In this report, we have examined the localization of the Dab2 protein in the mouse embryonic central nervous system (CNS) at different developmental stages. Results: Dab2 protein was transiently expressed in rhombomeres 5 and 6 of the developing hindbrain between E8.5 and E11.5, and in the floor plate of the neural tube from E9.5 to E12.5, following which it was no longer detectable within these regions. Dab2 protein was also identified within circumventricular organs including the choroid plexus, subcommissural organ and pineal gland during their early development. While Dab2 was still strongly expressed in the adult choroid plexus, immunoreactivity within the subcommissural organ and pineal gland was lost after birth. In addition, Dab2 was transiently expressed within a subpopulation of Iba1-positive mononuclear phagocytes (including presumed microglial progenitors) within the neural tube from E10.0 and was lost by E14.5. Dab2 was separately localized to Iba1 positive cells from E9.5 and subsequently to F4/80 positive cells (mature macrophage/myeloid-derived dendritic cells) positioned outside the neural tube from E12.5 onwards, implicating Dab2 expression in early cells of the mononuclear phagocyte lineage. Dab2 did not co-localize with the pan-neuronal marker PGP9.5 at any developmental stage, suggesting that Dab2 positive cells in the developing CNS are unlikely to be differentiating neurons. Conclusion: This is the first study to demonstrate the dynamic spatiotemporal expression of Dab2 protein within the CNS during development.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This study maps Dab2 protein expression in the developing mouse central nervous system and shows that it is dynamically and transiently expressed in non-neuronal cells, including hindbrain rhombomeres, floor plate, circumventricular organs, and mononuclear phagocytes. It is the first detailed report of spatiotemporal Dab2 expression during mammalian CNS development.

Key findings

  • Dab2 was transiently expressed in rhombomeres 5 and 6 of the developing hindbrain between E8.5 and E11.5, and in the neural tube floor plate from E9.5 to E12.5; expression was no longer detectable in these regions afterward.
  • Dab2 was detected in developing circumventricular organs—choroid plexus, subcommissural organ, and pineal gland—but while it remained strongly expressed in the adult choroid plexus, immunoreactivity was lost in the subcommissural organ and pineal gland after birth.
  • Dab2 was transiently expressed in a subpopulation of Iba1-positive mononuclear phagocytes within the neural tube from E10.0 and was lost by E14.5; outside the neural tube, Dab2 localized to Iba1-positive cells from E9.5 and to F4/80-positive cells from E12.5 onward.
  • Dab2 did not co-localize with the pan-neuronal marker PGP9.5 at any developmental stage, suggesting Dab2-positive cells in the developing CNS are unlikely to be differentiating neurons.

Methods

  • Random-bred ICR mice were used; embryos from E7.5 to E18.0 were collected, with at least 5–10 embryos analyzed per developmental stage.
  • Dab2 protein localization was examined by immunohistochemistry on 7-μm wax sections using a monoclonal anti-p96/Dab2 antibody, with standard ABC/DAB detection and pre-adsorption or primary-antibody replacement controls; whole-mount immunohistochemistry was also performed.
  • Double immunofluorescence staining used antibodies against Dab2, Iba1, F4/80, and PGP9.5, with confocal microscopy for co-localization analysis.

Limitations

  • Stated by the authors: in the developing pineal gland, they could not rule out that interstitial cells, in addition to pinealocytes, express Dab2; the functional significance of transient Dab2 expression in the pineal gland remains to be investigated.
  • Evident from the text: the study is descriptive localization without functional perturbation or lineage tracing, so roles in CNS and myeloid development are largely inferred.
  • Evident from the text: the anti-p96/Dab2 antibody recognizes an N-terminal epitope shared by the three known Dab2 isoforms p96, p93, and p67, so the study cannot distinguish which isoform(s) are expressed in the reported sites.

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

Integrity signals

Registry

Crossref · 10.1186/1471-213x-8-76

Cites

64 of 64 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

3 of 47 cited sources checked · 1 supported · 0 flagged · accuracy not yet measured

Show all 69 claims

  • Probably not a substantial claim. 15
  • It may state two separate claims as one. 35
44 of 44
  • The paper relies on this without support.

    The presumptive subcommissural organ develops from the region of the roof plate of the diencephalon just anterior to the mesencephalon.

    “The presumptive subcommissural organ (SCO) develops from the region of the roof plate of the diencephalon just anterior to the mesencephalon (Fig 2H, H').”
  • The paper relies on this without support.

    PGP9.5 is a pan-neuronal marker.

    “Double immunofluorescent labeling of Dab2 and PGP9.5, a pan-neuronal marker, was performed in order to determine whether Dab2 was expressed in neurons or nerve fibers that were closely associated with the SCO.”
  • The paper relies on this without support.

    F4/80 antigen is a macrophage differentiation marker.

    “The macrophage differentiation marker, F4/80 antigen, began to be expressed weakly in these fetal macrophages located outside the neural tube at E12.5 and became prominent from E14.5 onwards.”
  • The paper relies on this without support.

    A protein's expression pattern in specific cell types and developmental stages indicates its functional importance.

    “Dynamic expression of Dab2 protein was detected in the neuroepithelium, blood vessels, circumventricular organs and mononuclear phagocytes (fetal macrophages, microglial progenitors), strongly suggesting that Dab2 is an important molecule during mammalian CNS and myeloid cell development.”
  • The paper relies on this without support.

    The very early ontogenetic differentiation of SCO secretory cells is crucial for the smooth circulation of CSF secreted from the choroid plexus during early development.

    “The very early ontogenetic differentiation of SCO secretory cells is crucial for the smooth circulation of CSF secreted from the choroid plexus during early development.”
  • The authors state this as an assumption.

    Copulation occurred around midnight, so that noon of the plug day can be designated as embryonic day 0.5 (E0.5).

    “The noon of the plug day was designated as embryonic day 0.5 (E0.5) assuming that copulation occurred around midnight.”
6 of 6

Citations

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Research works printed but not linked: 1

  1. Rezaie P: Microglia, from origins to differentiation, distribution and dynamics within the mammalian central nervous system. Trends in Glial Research - Basic and Applied. Edited by: Dheen ST, Ling EA. 2007, India , Research Signpost, 1-41.

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Metadata

Authors
Cheung, K.-K., Mok, S. C., Rezaie, P., & Chan, W. Y.
Affiliations
  • Hong Kong Polytechnic University (HK)
  • The University of Texas MD Anderson Cancer Center (US)
  • King's College London (GB)
  • Chinese University of Hong Kong (HK)
Corresponding author
Chan, Wood Yee
Venue
BMC Developmental Biology
Published
2008-08-04
Volume
8
Issue
1
Pages
76-76
ISSN
1471-213X (ISSN-L)
OpenAlex
W2075358654
Cited by
23
References
62
Citations by year
2025: 1 · 2024: 3 · 2021: 1 · 2020: 2 · 2018: 1 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 3
FWCI
0.66
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • BMC Developmental Biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Open Research Online - ORO (The Open University) (acceptedVersion)
  • PolyU Institutional Research Archive (Hong Kong Polytechnic University) (submittedVersion, cc-by)
Funders
  • U.S. Department of Health and Human Services
  • Chinese University of Hong Kong
  • National Cancer Institute (R33CA103595, P50CA165009)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Dab2, floor plate, circumventricular organs, choroid plexus, subcommissural organ, pineal gland, mononuclear phagocytes, macrophages, myeloid dendritic cells, spatiotemporal gene expression, neuronal development
MeSH terms
Animals, Brain, Embryo, Mammalian, Mice, Inbred ICR, Mononuclear Phagocyte System, Gene Expression Regulation, Developmental, Adaptor Proteins, Vesicular Transport, Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins, Mice, Neural Tube

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