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Cell Rep. 2017 May 16;19(7):1378-1393. doi: 10.1016/j.celrep.2017.04.056.

CNS Macrophages Control Neurovascular Development via CD95L.

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Department of Molecular Neurobiology, German Cancer Research Center (DFKZ), 69120 Heidelberg, Germany.
Biochemistry Center, Heidelberg University, 69120 Heidelberg, Germany.
Institute of Pathophysiology, University Medical Center of Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
Department of Molecular Neurobiology, German Cancer Research Center (DFKZ), 69120 Heidelberg, Germany. Electronic address:


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.


CD95; CD95L; CNS macrophages; angiogenesis; cortex; microglia; neurovascular development; retina; vessel

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