4.7 Article

P130Cas/bcar1 mediates zebrafish caudal vein plexus angiogenesis

Journal

SCIENTIFIC REPORTS
Volume 10, Issue 1, Pages -

Publisher

NATURE RESEARCH
DOI: 10.1038/s41598-020-71753-w

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Funding

  1. British Heart Foundation [FS/16/41/32235, PG/18/34/337850, SP/08/004]

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P130CAS/BCAR1 belongs to the CAS family of adaptor proteins, with important regulatory roles in cell migration, cell cycle control, and apoptosis. Previously, we and others showed that P130CAS mediates VEGF-A and PDGF signalling in vitro, but its cardiovascular function in vivo remains relatively unexplored. We characterise here a novel deletion model of P130CAS in zebrafish. Using in vivo microscopy and transgenic vascular reporters, we observed that while bcar1-/- zebrafish showed no arterial angiogenic or heart defects during development, they strikingly failed to form the caudal vein plexus (CVP). Endothelial cells (ECs) within the CVP of bcar1-/- embryos produced fewer filopodial structures and did not detach efficiently from neighbouring cells, resulting in a significant reduction in ventral extension and overall CVP area. Mechanistically, we show that P130Cas mediates Bmp2b-induced ectopic angiogenic sprouting of ECs in the developing embryo and provide pharmacological evidence for a role of Src family kinases in CVP development.

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