HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 69/6/1852    most recent biolreprod.103.019612v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Duan, L.-J. Articles by Fong, G.-H. Search for Related Content PubMed PubMed Citation Articles by Duan, L.-J. Articles by Fong, G.-H. Agricola Articles by Duan, L.-J. Articles by Fong, G.-H.

Gastrulation and Angiogenesis, Not Endothelial Specification, Is Sensitive to Partial Deficiency in Vascular Endothelial Growth Factor-A in Mice¹

Center for Vascular Biology,³ Departments of Physiology,⁴ Genetics and Developmental Biology,⁵ University of Connecticut Health Center, Farmington, Connecticut 06030 Samuel Lunenfeld Research Institute,⁶ Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5

Mouse embryogenesis is dose sensitive to vascular endothelial growth factor-A (VEGF-A), and mouse embryos partially deficient in VEGF-A die in utero because of severe vascular defects. In this study, we investigate the possible causes that underlie this phenomenon. Although the development of vascular defects in VEGF-A-deficient embryos seems to suggest that endothelial differentiation depends on the presence of a sufficient level of VEGF-A, we were surprised to find that endothelial differentiation per se is insensitive to a significant loss of VEGF-A activity. Instead, the development of the multipotent mesenchymal cells, from which endothelial progenitors arise in the yolk sac, is most highly dependent on VEGF-A. As a result of VEGF-A deficiency, dramatically fewer multipotent mesenchymal cells are generated in the prospective yolk sac. However, among the small number of mesenchymal cells that do enter the prospective yolk sac, endothelial differentiation occurs at a normal frequency. In the embryo proper, vasculogenesis is initiated actively in spite of a significant VEGF-A deficiency, but the subsequent steps of vascular development are defective. We conclude that a full-level VEGF-A activity is not critical for endothelial specification but is important for two distinct processes before and after endothelial specification: the development of the yolk sac mesenchyme and angiogenic sprouting of blood vessels.

¹ Supported by U.S. Public Health grant 5R01 HL68168 02 to G-H.F.

² Correspondence: Guo-Hua Fong, Center for Vascular Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3501. FAX: 860 679 1201; fong{at}nso2.uchc.edu