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Cell Rep ; 34(1): 108587, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33406432

RESUMO

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.


Assuntos
Embrião de Mamíferos/metabolismo , Células Ependimogliais/fisiologia , Hipotálamo/embriologia , Hipotálamo/fisiologia , Microglia/fisiologia , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , c-Mer Tirosina Quinase/metabolismo , Animais , Encéfalo/embriologia , Desenvolvimento Embrionário , Regulação da Expressão Gênica no Desenvolvimento , Imunidade Inata , Camundongos , Camundongos Transgênicos , Imagem Óptica/métodos , Receptor Tirosina Quinase Axl
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