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First published online 4 August 2004
doi: 10.1242/dev.01304

Development 131, 4371-4380 (2004)
Published by The Company of Biologists 2004
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Hedgehog signaling is essential for endothelial tube formation during vasculogenesis

Steven A. Vokes1,*, Tatiana A. Yatskievych1, Ronald L. Heimark2, Jill McMahon3, Andrew P. McMahon3, Parker B. Antin1 and Paul A. Krieg1,{dagger}

1 Department of Cell Biology and Anatomy, University of Arizona Health Sciences Center, 1501 North Campbell Avenue, Tucson, AZ 85724-5044, USA
2 Department of Surgery, University of Arizona Health Sciences Center, 1501 North Campbell Avenue, Tucson, AZ 85724-5044, USA
3 Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA

{dagger} Author for correspondence (e-mail: pkrieg{at}email.arizona.edu)

Accepted 9 June 2004

During embryonic development, the first blood vessels are formed through the aggregation and subsequent assembly of angioblasts (endothelial precursors) into a network of endothelial tubes, a process known as vasculogenesis. These first vessels generally form in mesoderm that is adjacent to endodermal tissue. Although specification of the angioblast lineage is independent of endoderm interactions, a signal from the endoderm is necessary for angioblasts to assemble into a vascular network and to undergo vascular tube formation. In this study, we show that endodermally derived sonic hedgehog is both necessary and sufficient for vascular tube formation in avian embryos. We also show that Hedgehog signaling is required for vascular tube formation in mouse embryos, and for vascular cord formation in cultured mouse endothelial cells. These results demonstrate a previously uncharacterized role for Hedgehog signaling in vascular development, and identify Hedgehog signaling as an important component of the molecular pathway leading to vascular tube formation.

Key words: Vasculogenesis, Tubulogenesis, Endoderm, VEGF, Mouse, Chick


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