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First published online August 25, 2008
doi: 10.1242/10.1242/dev.019919

Development 135, 3161-3171 (2008)
Published by The Company of Biologists 2008
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Hedgehog signaling to distinct cell types differentially regulates coronary artery and vein development

Kory J. Lavine1, Fanxin Long1,3, Kyunghee Choi2, Craig Smith1 and David M. Ornitz1,*

1 Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA.
2 Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
3 Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.

* Author for correspondence (e-mail: dornitz{at}wustl.edu)

Accepted 16 July 2008

Vascular development begins with formation of a primary capillary plexus that is later remodeled to give rise to the definitive vasculature. Although the mechanism by which arterial and venous fates are acquired is well understood, little is known about when during vascular development arterial and venous vessels emerge and how their growth is regulated. Previously, we have demonstrated that a hedgehog (HH)/vascular endothelial growth factor (VEGF) and angiopoeitin 2 (ANG2) signaling pathway is essential for the development of the coronary vasculature. Here, we use conditional gene targeting to identify the cell types that receive HH signaling and mediate coronary vascular development. We show that HH signaling to the cardiomyoblast is required for the development of coronary veins, while HH signaling to the perivascular cell (PVC) is necessary for coronary arterial growth. Moreover, the cardiomyoblast and PVC appear to be the exclusive cell types that receive HH signals, as ablation of HH signaling in both cell types leads to an arrest in coronary development. Finally, we present evidence suggesting that coronary arteries and veins may be derived from distinct lineages.

Key words: Hedgehog (HH), Vascular endothelial growth factor (VEGF), Angiopoietin (ANG), Heart development, Coronary vascular development, Myocardium, Pericyte




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