The Role of Egfl7 in Vascular Morphogenesis

  1. Derek J. Chadwick Organizer and
  2. Jamie Goode
  1. Maike Schmidt1,
  2. Ann De Mazière2,
  3. Tanya Smyczek1,
  4. Alane Gray3,
  5. Leon Parker2,
  6. Ellen Filvaroff4,
  7. Dorothy French5,
  8. Suzanne van Dijk2,
  9. Judith Klumperman2 and
  10. Weilan Ye1,†

Published Online: 11 SEP 2007

DOI: 10.1002/9780470319413.ch3

Vascular Development: Novartis Foundation Symposium 283

Vascular Development: Novartis Foundation Symposium 283

How to Cite

Schmidt, M., De Mazière, A., Smyczek, T., Gray, A., Parker, L., Filvaroff, E., French, D., van Dijk, S., Klumperman, J. and Ye, W. (2007) The Role of Egfl7 in Vascular Morphogenesis, in Vascular Development: Novartis Foundation Symposium 283 (eds D. J. Chadwick and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9780470319413.ch3

Author Information

  1. 1

    Tumor Biology and Angiogenesis Department Genentech Inc. 1 DNA Way, South San Francisco, CA 94080, USA

  2. 2

    Cell Microscopy Center, Department of Cell Biology and Institute for Biomembranes, University Medical Center, Utrecht, 3584C, Utrecht, The Netherlands

  3. 3

    Molecular Biology Department Genentech Inc. 1 DNA Way, South San Francisco, CA 94080, USA

  4. 4

    Molecular Oncology Department Genentech Inc. 1 DNA Way, South San Francisco, CA 94080, USA

  5. 5

    Pathology Department, Genentech Inc. 1 DNA Way, South San Francisco, CA 94080, USA

  1. This paper was presented at the symposium by Weilan Ye, to whom correspondence should be addressed.

Publication History

  1. Published Online: 11 SEP 2007
  2. Published Print: 20 JUL 2007

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470034286

Online ISBN: 9780470319413

SEARCH

Keywords:

  • Egfl7;
  • Endothelial Cells;
  • Extracellular Matrix;
  • Vasculature;
  • Morphogenesis;
  • Tubulogenesis;
  • VE-Statin;
  • EC Migration;
  • EC Connections;
  • Angiogenesis

Summary

EGFL7 was identified by a number of groups as a putative secreted factor produced by the vascular endothelial cells (ECs). In a recent publication, we showed that EGFL7 regulates midline angioblast migration in zebrafish embryos—a key step in vascular tubulogenesis. In this study, we further characterized the zebrafish vasculature in the Egfl7 knockdown embryos at the ultrastructural level, and found that malformation of axial vessels is indeed due to the accumulation of angioblasts and aberrant connection among themselves, but not abnormal interaction between ECs and other cell types. Using in vitro biochemical assays, we demonstrated that EGFL7 is tightly associated with the extracellular matrix (ECM), and it supports EC migration either as a single factor or in combination with other ECM molecules. In order to evaluate if the biological function of EGFL7 is evolutionarily conserved, we generated Egfl7 knockout mice and analysed vascular development in a number of tissues. We found that vascular coverage of a given tissue is reduced or delayed, and vascular morphogenesis is defective in the Egfl7 mutant mice. Taken together, we conclude that EGFL7 provides a proper microenvironment for endothelial cell migration, thereby enabling accurate patterning. Our study indicates that the molecular composition of the ECM influences vascular morphogenesis.