Endothelial expression of the Notch ligand Jagged1 is required for vascular smooth muscle development

doi:10.1073/pnas.0709663105

Endothelial expression of the Notch ligand Jagged1 is required for vascular smooth muscle development

*Department of Cell and Developmental Biology and Cardiovascular Institute,
^†Abramson Family Cancer Research Institute, Institute for Medicine and Engineering, and Department of Pathology and Laboratory Medicine, and
^¶Department of Genetics and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104;
^‡Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital, Philadelphia, PA 19104; and
^§Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104

Edited by Eric N. Olson, University of Texas Southwestern Medical Center, Dallas, TX, and approved December 18, 2007 (received for review October 10, 2007)

Abstract

The Notch ligand Jagged1 (Jag1) is essential for vascular remodeling and has been linked to congenital heart disease in humans, but its precise role in various cell types of the cardiovascular system has not been extensively investigated. We show that endothelial-specific deletion of Jag1 results in embryonic lethality and cardiovascular defects, recapitulating the Jag1 null phenotype. These embryos show striking deficits in vascular smooth muscle, whereas endothelial Notch activation and arterial-venous differentiation appear normal. Endothelial Jag1 mutant embryos are phenotypically distinct from embryos in which Notch signaling is inhibited in endothelium. Together, these results imply that the primary role of endothelial Jag1 is to potentiate the development of neighboring vascular smooth muscle.

Footnotes

^‖To whom correspondence should be addressed. E-mail: epsteinj{at}mail.med.upenn.edu
Author contributions: F.A.H. and J.A.E. designed research; F.A.H. and M.M.L. performed research; W.S.P., K.M.L., and K.H.K. contributed new reagents/analytic tools; F.A.H. analyzed data; and F.A.H. and J.A.E. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0709663105/DC1.