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Publication : Vascular FLRT2 regulates venous-mediated angiogenic expansion and CNS barriergenesis.

First Author  Llaó-Cid C Year  2024
Journal  Nat Commun Volume  15
Issue  1 Pages  10372
PubMed ID  39609404 Mgi Jnum  J:360756
Mgi Id  MGI:7786053 Doi  10.1038/s41467-024-54570-x
Citation  Llao-Cid C, et al. (2024) Vascular FLRT2 regulates venous-mediated angiogenic expansion and CNS barriergenesis. Nat Commun 15(1):10372
abstractText  Veins have emerged as the origin of all other endothelial cell subtypes needed to expand vascular networks during developmental and pathological neoangiogenesis. Here, we uncover the role of the angioneurin Fibronectin Leucine Rich Transmembrane protein (FLRT) 2 in central nervous system (CNS) vascular development in the mouse. Early postnatal FLRT2 deletion reveals specific defects in retinal veins, impacting endothelial cell proliferation, sprouting and polarity that result in reduced tip cells at the vascular front. FLRT2 interacts with VE-cadherin and together with the endocytic adaptor protein Numb contribute to the modulation of adherens junction morphology in both retina and cerebral cortex in vivo. Utilizing expansion microscopy, we visualize the altered dynamic distribution of VE-cadherin in tissue of FLRT2 endothelial mutants. Additionally, FLRT2 in cortical vessels regulates the crosstalk between adherens and tight junctions, influencing blood-brain barrier development. Our findings position FLRT2 as a vein-specific regulator of CNS vascular development.
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