CNS Macrophages Control Neurovascular Development via CD95L

Cell Reports
Si ChenAna Martin-Villalba

Abstract

The development of neurons and vessels shares striking anatomical and molecular features, and it is presumably orchestrated by an overlapping repertoire of extracellular signals. CNS macrophages have been implicated in various developmental functions, including the morphogenesis of neurons and vessels. However, whether CNS macrophages can coordinately influence neurovascular development and the identity of the signals involved therein is unclear. Here, we demonstrate that activity of the cell surface receptor CD95 regulates neuronal and vascular morphogenesis in the post-natal brain and retina. Furthermore, we identify CNS macrophages as the main source of CD95L, and macrophage-specific deletion thereof reduces both neurovascular complexity and synaptic activity in the brain. CD95L-induced neuronal and vascular growth is mediated through src-family kinase (SFK) and PI3K signaling. Together, our study highlights a coordinated neurovascular development instructed by CNS macrophage-derived CD95L, and it underlines the importance of macrophages for the establishment of the neurovascular network during CNS development.

Citations

Aug 30, 2018·Physiological Reviews·Vanessa Frodermann, Matthias Nahrendorf
Aug 28, 2019·The Journal of Clinical Investigation·Nathalie TischCarmen Ruiz de Almodovar
Jun 1, 2018·Annual Review of Vision Science·Sean M Silverman, Wai T Wong
Apr 25, 2019·International Journal of Molecular Sciences·Jung Min Lee
Jan 1, 2020·Neural Development·Fenge LiMelanie A Samuel
Jan 13, 2021·Cell and Tissue Research·Takehito SatoHiroshi Kiyama
Mar 31, 2021·Cellular and Molecular Life Sciences : CMLS·Nathalie Tisch, Carmen Ruiz de Almodóvar

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