P130Cas/bcar1 mediates zebrafish caudal vein plexus angiogenesis

Area of Science:

• Cardiovascular Biology
• Developmental Biology
• Cell Biology

Background:

• P130CAS (BCAR1) is a CAS family adaptor protein involved in cell migration, cell cycle control, and apoptosis.
• Previous studies demonstrated P130CAS involvement in VEGF-A and PDGF signaling in vitro.
• The in vivo cardiovascular function of P130CAS remains largely uncharacterized.

Purpose of the Study:

• To investigate the in vivo cardiovascular role of P130CAS using a novel zebrafish deletion model.
• To elucidate the specific defects in vascular development caused by the absence of P130CAS.

Main Methods:

• Generation and characterization of a P130CAS/BCAR1 deletion mutant zebrafish model.
• In vivo microscopy and transgenic vascular reporters to visualize vascular development.
• Analysis of endothelial cell behavior, including filopodial structure formation and cell detachment.

Main Results:

• Zebrafish lacking P130CAS (bcar1-/-) showed normal arterial development and heart function but failed to form the caudal vein plexus (CVP).
• Endothelial cells in bcar1-/- embryos exhibited reduced filopodial structures and impaired detachment, leading to decreased ventral extension and CVP area.
• P130Cas was found to mediate Bmp2b-induced angiogenic sprouting and Src family kinases were implicated in CVP development.

Conclusions:

• P130CAS (BCAR1) plays a critical, previously unrecognized role in the development of the caudal vein plexus (CVP) in vivo.
• Defects in endothelial cell migration and detachment underlie the CVP formation failure in P130CAS-deficient zebrafish.
• This study highlights P130CAS as a key regulator of angiogenesis in the context of CVP development.