Specialized endothelial tip cells guide neuroretina vascularization and blood-retina-barrier formation.

Dev Cell

Centre de Recherche, CHU St. Justine, Montréal, QC H3T 1C5, Canada; Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montréal, QC H3T 1J4, Canada. Electronic address:

Published: August 2021

Endothelial tip cells guiding tissue vascularization are primary targets for angiogenic therapies. Whether tip cells require differential signals to develop their complex branching patterns remained unknown. Here, we show that diving tip cells invading the mouse neuroretina (D-tip cells) are distinct from tip cells guiding the superficial retinal vascular plexus (S-tip cells). D-tip cells have a unique transcriptional signature, including high TGF-β signaling, and they begin to acquire blood-retina barrier properties. Endothelial deletion of TGF-β receptor I (Alk5) inhibits D-tip cell identity acquisition and deep vascular plexus formation. Loss of endothelial ALK5, but not of the canonical SMAD effectors, leads to aberrant contractile pericyte differentiation and hemorrhagic vascular malformations. Oxygen-induced retinopathy vasculature exhibits S-like tip cells, and Alk5 deletion impedes retina revascularization. Our data reveal stage-specific tip cell heterogeneity as a requirement for retinal vascular development and suggest that non-canonical-TGF-β signaling could improve retinal revascularization and neural function in ischemic retinopathy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9951594PMC
http://dx.doi.org/10.1016/j.devcel.2021.06.021DOI Listing

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