Endothelial cell migration during murine yolk sac vascular remodeling occurs via a Rac1 and FAK activation pathway in vivo

• Published in: Developmental dynamics 2010-10, Vol.239 (10), p.2570-2583
• Main Authors: Enciso, Josephine M., Konecny, Christine M., Karpen, Heidi E., Hirschi, Karen K.
• Format: Article
• Language: English
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.22389

The molecular mechanism(s) controlling cell migration during vascular morphogenesis in vivo remain largely undefined. To address this within a physiological context, we employed retinaldehyde dehydrogenase-2 ( Raldh 2) null mouse embryos and demonstrate that retinoic acid (RA) deficiency results in abnormal yolk sac vascular remodeling due to decreased Rac1 activation, increased RhoA activation, and increased focal adhesions. Vinculin was increased in Raldh2 −/− yolk sacs, and molecular events important for focal adhesion turnover, FAK phosphorylation (Tyr397) and FAK-paxillin association, were decreased. RA-rescue of vascular remodeling downregulated vinculin and restored FAK phosphorylation (Tyr397) and FAK-paxillin association. Further, vascular rescue with VEGF-A, Indian hedgehog, and bFGF restored FAK phosphorylation (Tyr397) in the endothelium of Raldh2 −/− yolk sacs. Our results provide new insights into the regulation of endothelial cell migration during vascular remodeling in vivo by adding the Rac1 and FAK activation pathway as a critical mediator of focal adhesion formation and turnover during vascular remodeling.