Developmental Cell
Volume 11, Issue 1, July 2006, Pages 81-92
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Article
HIF-Dependent Hematopoietic Factors Regulate the Development of the Embryonic Vasculature

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Summary

Hypoxia inducible factors (HIFs) regulate adaptive responses to changes in oxygen (O2) tension during embryogenesis, tissue ischemia, and tumorigenesis. Because HIF-deficient embryos exhibit a number of developmental defects, the precise role of HIF in early vascular morphogenesis has been uncertain. Using para-aortic splanchnopleural (P-Sp) explant cultures, we show that deletion of the HIF-β subunit (ARNT) results in defective hematopoiesis and the inhibition of both vasculogenesis and angiogenesis. These defects are rescued upon the addition of wild-type Sca-1+ hematopoietic cells or recombinant VEGF. Arnt−/− embryos exhibit reduced levels of VEGF protein and increased numbers of apoptotic hematopoietic cells. These results suggest that HIF coordinates early endothelial cell emergence and vessel development by promoting hematopoietic cell survival and paracrine growth factor production.

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These authors contributed equally to this work.

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Present address: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, The Children's Hospital of Philadelphia, Abramson Research Center Room 516I, 3615 Civic Center Boulevard., Philadelphia, Pennsylvania 19104.