Radial Glia Cells Control Angiogenesis in the Developing Cerebral Cortex Through TGF-β1 Signaling

Molecular Neurobiology
Michele SiqueiraJoice Stipursky

Abstract

Neuroangiogenesis in the developing central nervous system is controlled by interactions between endothelial cells (ECs) and radial glia (RG) neural stem cells, although RG-derived molecules implicated in these events are not fully known. Here, we investigated the role of RG-secreted TGF-β1, in angiogenesis in the developing cerebral cortex. By isolation of murine microcapillary brain endothelial cells (MBECs), we demonstrate that conditioned medium from RG cultures (RG-CM) promoted MBEC migration and formation of vessel-like structures in vitro, in a TGF-β1-dependent manner. These events were followed by endothelial regulation of GPR124 and BAI-1 gene expression by RG-CM. Proteome profile of RG-CM identified angiogenesis-related molecules IGFBP2/3, osteopontin, endostatin, SDF1, fractalkine, TIMP1/4, Ang-1, pentraxin3, and Cyr61, some of them modulated by TGF-β1 induction. In vivo gain and loss of function assays targeting RG cells demonstrates a specific TGF-β1-dependent control of blood vessels branching in the cerebral cortex. Together, our results point to TGF-β1 signaling pathway as a potential mediator of the RG-EC interactions and shed light to the key role of RG in paving the brain vascular network.

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Citations

Nov 1, 2018·Molecular Neurobiology·Luan Pereira DinizFlávia Carvalho Alcantara Gomes
May 10, 2020·Journal of Neural Transmission·Philipp WörsdörferSüleyman Ergün
Apr 4, 2019·Frontiers in Aging Neuroscience·Isadora MatiasFlávia Carvalho Alcantara Gomes
May 3, 2020·Development·Saptarshi BiswasDritan Agalliu
Jan 30, 2019·Translational Stroke Research·Jyoti GautamYao Yao
Oct 20, 2020·Frontiers in Cell and Developmental Biology·Yizhe Zhang, Xiao Yang
Dec 17, 2020·International Journal of Molecular Sciences·Daniele LanaMaria Grazia Giovannini
Mar 11, 2021·Cellular and Molecular Life Sciences : CMLS·Timothy J A Chico, Elisabeth C Kugler

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Methods Mentioned

BETA
Assay
antisense oligonucleotides
electrophoresis
PCR
Antibody Array
nuclear translocation
transfection

Software Mentioned

ImageJ
GraphPad Prism
AngioTool
Adobe Photoshop

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