Tags

Type your tag names separated by a space and hit enter

Endogenous microglia regulate development of embryonic cortical precursor cells.

Abstract

Microglia play important roles in the damaged or degenerating adult nervous system. However, the role of microglia in embryonic brain development is still largely uncharacterized. Here we show that microglia are present in regions of the developing brain that contain neural precursors from E11 onward. To determine whether these microglia are important for neural precursor maintenance or self-renewal, we cultured embryonic neural precursors from the cortex of PU.1(-/-) mice, which we show lack resident microglia during embryogenesis. Cell survival and neurogenesis were similar in cultures from PU.1(-/-) vs. PU.1(+/+) mice, but precursor proliferation and astrogenesis were both reduced. Cortical precursors depleted of microglia also displayed decreased precursor proliferation and astrogenesis, and these deficits could be rescued when microglia were added back to the cultures. Moreover, when the number of microglia present in cortical precursor cultures was increased above normal levels, astrogenesis but not neurogenesis was increased. Together these results demonstrate that microglia present within the embryonic neural precursor niche can regulate neural precursor development and suggest that alterations in microglial number as a consequence of genetic or pathological events could perturb neural development by directly affecting embryonic neural precursors.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Developmental and Stem Cell Biology Program, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. joseph.antony@utoronto.ca

    , , ,

    Source

    Journal of neuroscience research 89:3 2011 Mar pg 286-98

    MeSH

    Age Factors
    Animals
    Calcium-Binding Proteins
    Cell Differentiation
    Cell Proliferation
    Cells, Cultured
    Cerebral Cortex
    Cerebral Ventricles
    Embryo, Mammalian
    Glial Fibrillary Acidic Protein
    Green Fluorescent Proteins
    Intermediate Filament Proteins
    Ki-67 Antigen
    Mice
    Mice, Transgenic
    Microfilament Proteins
    Microglia
    Nerve Tissue Proteins
    Nestin
    Neurogenesis
    Neurons
    O Antigens
    Proto-Oncogene Proteins
    Stem Cells
    Trans-Activators
    Tubulin

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21259316

    Citation

    Antony, Joseph M., et al. "Endogenous Microglia Regulate Development of Embryonic Cortical Precursor Cells." Journal of Neuroscience Research, vol. 89, no. 3, 2011, pp. 286-98.
    Antony JM, Paquin A, Nutt SL, et al. Endogenous microglia regulate development of embryonic cortical precursor cells. J Neurosci Res. 2011;89(3):286-98.
    Antony, J. M., Paquin, A., Nutt, S. L., Kaplan, D. R., & Miller, F. D. (2011). Endogenous microglia regulate development of embryonic cortical precursor cells. Journal of Neuroscience Research, 89(3), pp. 286-98. doi:10.1002/jnr.22533.
    Antony JM, et al. Endogenous Microglia Regulate Development of Embryonic Cortical Precursor Cells. J Neurosci Res. 2011;89(3):286-98. PubMed PMID: 21259316.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Endogenous microglia regulate development of embryonic cortical precursor cells. AU - Antony,Joseph M, AU - Paquin,Annie, AU - Nutt,Stephen L, AU - Kaplan,David R, AU - Miller,Freda D, Y1 - 2011/01/06/ PY - 2010/08/12/received PY - 2010/09/02/revised PY - 2010/09/16/accepted PY - 2011/1/25/entrez PY - 2011/1/25/pubmed PY - 2011/5/4/medline SP - 286 EP - 98 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 89 IS - 3 N2 - Microglia play important roles in the damaged or degenerating adult nervous system. However, the role of microglia in embryonic brain development is still largely uncharacterized. Here we show that microglia are present in regions of the developing brain that contain neural precursors from E11 onward. To determine whether these microglia are important for neural precursor maintenance or self-renewal, we cultured embryonic neural precursors from the cortex of PU.1(-/-) mice, which we show lack resident microglia during embryogenesis. Cell survival and neurogenesis were similar in cultures from PU.1(-/-) vs. PU.1(+/+) mice, but precursor proliferation and astrogenesis were both reduced. Cortical precursors depleted of microglia also displayed decreased precursor proliferation and astrogenesis, and these deficits could be rescued when microglia were added back to the cultures. Moreover, when the number of microglia present in cortical precursor cultures was increased above normal levels, astrogenesis but not neurogenesis was increased. Together these results demonstrate that microglia present within the embryonic neural precursor niche can regulate neural precursor development and suggest that alterations in microglial number as a consequence of genetic or pathological events could perturb neural development by directly affecting embryonic neural precursors. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/21259316/Endogenous_microglia_regulate_development_of_embryonic_cortical_precursor_cells_ L2 - https://doi.org/10.1002/jnr.22533 DB - PRIME DP - Unbound Medicine ER -