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© The Rockefeller University Press, 0021-9525/2000//343 $5.00
The Journal of Cell Biology, Volume 148, Number 2, , 2000 343-352

Original Article

Homeobox B3 Promotes Capillary Morphogenesis and Angiogenesis



Connie Myersa, Aubri Charboneaub, and Nancy Boudreaua

a Surgical Research Laboratories, University of California San Francisco, San Francisco, California 94143
b Department of Anatomy, Medical College of Virginia, Richmond, Virginia 23298
Surgical Research Laboratories, Box 1302, University of California San Francisco, San Francisco, CA 94143.(415) 206-6997(415) 206-6951

nancyjb{at}itsa.ucsf.edu

Endothelial cells (EC) express several members of the Homeobox (Hox) gene family, suggesting a role for these morphoregulatory mediators during angiogenesis. We have previously established that Hox D3 is required for expression of integrin {alpha}vβ3 and urokinase plasminogen activator (uPA), which contribute to EC adhesion, invasion, and migration during angiogenesis. We now report that the paralogous gene, Hox B3, influences angiogenic behavior in a manner that is distinct from Hox D3. Antisense against Hox B3 impaired capillary morphogenesis of dermal microvascular EC cultured on basement membrane extracellular matrices. Although levels of Hox D3-dependent genes were maintained in these cells, levels of the ephrin A1 ligand were markedly attenuated. Capillary morphogenesis could be restored, however, by addition of recombinant ephrin A1/Fc fusion proteins. To test the impact of Hox B3 on angiogenesis in vivo, we constitutively expressed Hox B3 in the chick chorioallantoic membrane using avian retroviruses that resulted in an increase in vascular density and angiogenesis. Thus, while Hox D3 promotes the invasive or migratory behavior of EC, Hox B3 is required for the subsequent capillary morphogenesis of these new vascular sprouts and, together, these results support the hypothesis that paralogous Hox genes perform complementary functions within a particular tissue type.

Key Words: endothelial cells • Hox • neovascularization • extracellular matrix • ephrin

© 2000 The Rockefeller University Press

Abbreviations used in this paper: bFGF, basic fibroblast growth factor; BM, basement membrane; CAM, chick chorioallantoic membrane; EC, endothelial cells; ECM, extracellular matrix; HMEC, human microvascular endothelial cells; HMEC-1, human dermal microvascular endothelial cells; Hox, Homeobox; RT, reverse transcriptase; uPA, urokinase plasminogen activator.


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