期刊
CELL REPORTS
卷 34, 期 1, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2020.108587
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类别
资金
- Canadian Institutes of Health Research (CIHR) [MEF-140891]
- Alberta Children's Research Institute (ACHRI)
- Alberta Innovates (AI)
- Hotchkiss Brain Institute (HBI)
- Graduate Scholarship from HBI
- Undergraduate Scholarship from the Natural Sciences and Engineering Research Council (NSERC)
- CIHR/ACHRI training grant in Genetics, Child Health and Development
- CIHR operating grant [MOP-275053]
This study found that embryonic microglia show a strong responsiveness to insults during gestation, coordinating an innate immune response and playing a crucial role in the critical window for neurodevelopment.
Despite a growing appreciation for microglial influences on the developing brain, the responsiveness of microglia to insults during gestation remains less well characterized, especially in the embryo when microglia themselves are still maturing. Here, we asked if fetal microglia could coordinate an innate immune response to an exogenous insult. Using time-lapse imaging, we showed that hypothalamic microglia actively surveyed their environment by near-constant touching'' of radial glia projections. However, following an insult (i.e., IUE or AAV transduction), this seemingly passive touching became more intimate and long lasting, ultimately resulting in the retraction of radial glial projections and degeneration into small pieces. Mechanistically, the TAM receptors MERTK and AXL were upregulated in microglia following the insult, and Annexin V treatment inhibited radial glia breakage and engulfment by microglia. These data demonstrate a remarkable responsiveness of embryonic microglia to insults during gestation, a critical window for neurodevelopment.
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