Endothelial cell migration during murine yolk sac vascular remodeling occurs by means of a rac1 and FAK activation pathway in vivo

Authors

  • Josephine M. Enciso,

    Corresponding author
    1. Division of Neonatology, Department of Pediatrics, University of California, Los Angeles, Los Angeles, California
    • 10833 Le Conte Avenue, MDCC B2-375, Los Angeles, CA 90095
    Search for more papers by this author
  • Christine M. Konecny,

    1. Department of Pediatrics, Baylor College of Medicine, Houston, Texas
    2. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas
    Search for more papers by this author
  • Heidi E. Karpen,

    1. Department of Pediatrics, Baylor College of Medicine, Houston, Texas
    Search for more papers by this author
  • Karen K. Hirschi

    1. Department of Pediatrics, Baylor College of Medicine, Houston, Texas
    2. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas
    3. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas
    4. Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas
    Search for more papers by this author

Abstract

The molecular mechanism(s) controlling cell migration during vascular morphogenesis in vivo remain largely undefined. To address this within a physiological context, we used retinaldehyde dehydrogenase-2 (Raldh2) 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 down-regulated vinculin and restored FAK phosphorylation (Tyr397) and FAK-paxillin association. Furthermore, vascular rescue with vascular endothelial growth factor-A, Indian hedgehog, and basic fibroblast growth factor 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. Developmental Dynamics 239:2570–2583, 2010. © 2010 Wiley-Liss, Inc.

Ancillary