Signaling pathways that regulate blood vessel morphogenesis

• Published in: The FASEB journal 2006-03, Vol.20 (4), p.A22-A22
• Main Authors: Bautch, Victoria L, Roberts, D M, Kappas, N C, Taylor, S M, Stanford, W L, Fried, J H, Randhawa, L, Zeng, G
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.20.4.A22-a

We study how signals are integrated to regulate morphogenetic processes during blood vessel formation, and how cell division and morphogenesis are co‐ordinated. We utilize a stem cell model that allows for in vitro formation of blood vessels via vasculogenesis and angiogenic sprouting. We have incorporated GFP reporters into the developing vessels for dynamic imaging. Using these reagents, we have studied the role of the VEGF receptor flt‐1 (VEGFR‐1) in vessel morphogenesis using cells lacking flt‐1. Our data shows that flt‐1 normally negatively regulates endothelial cell division, but it positively regulates sprouting morphogenesis. This occurs primarily through the activity of a soluble form of the receptor (sflt‐1), as rescue with this isoform is more efficient than rescue with membrane‐localized isoforms. We also investigate the role of a Ras/Rap activator called RasGRP3. RasGRP3 is a novel endothelial DAG/phorbol ester receptor that mediates a florid dysmorphogenesis upon treatment of embryonic vessels with phorbol esters. The pathway downstream of RasGRP3 resembles a pathway that leads to vessel permeability. Thus we hypothesize that RasGRP3, which is not required for viability, is important in pathological situations to regulate permeability. RasGRP3 expression is regulated by VEGF, and we are currently investigating whether it is functionally downstream of effects of VEGF on morphogenesis and permeability.