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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates

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Endogenous microglia regulate development of embryonic cortical precursor cells.

Joseph M Antony¹, Annie Paquin, Stephen L Nutt

¹Developmental and Stem Cell Biology Program, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. joseph.antony@utoronto.ca

Journal of Neuroscience Research

|January 25, 2011

Summary

Embryonic microglia regulate neural precursor development. Depletion reduces precursor proliferation and astrogenesis, highlighting microglia

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Area of Science:

Neuroscience
Developmental Biology
Immunology

Background:

Microglia are key in adult nervous system repair.
Their role in embryonic brain development is largely unknown.

Purpose of the Study:

Investigate the function of microglia in embryonic neural precursor maintenance and self-renewal.
Determine if microglia influence neural precursor proliferation, survival, and differentiation.

Main Methods:

Cultured embryonic neural precursors from PU.1(-/-) mice (lacking microglia) and wild-type (PU.1(+/+)) littermates.
Assessed cell survival, proliferation, neurogenesis, and astrogenesis in vitro.
Manipulated microglial numbers in cultures to observe effects on neural precursors.

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Main Results:

PU.1(-/-) precursors showed reduced proliferation and astrogenesis compared to PU.1(+/+) precursors.
Microglia depletion in cortical precursors decreased proliferation and astrogenesis.
Adding microglia back rescued these deficits; increased microglia enhanced astrogenesis.

Conclusions:

Embryonic microglia regulate neural precursor proliferation and astrogenesis within the developing brain niche.
Altered microglial numbers can impact neural development by affecting embryonic neural precursors.