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Homeobox B3 promotes capillary morphogenesis and angiogenesis.
C Myers1, A Charboneau, N Boudreau
1Surgical Research Laboratories, University of California San Francisco, San Francisco, California 94143, USA.
The Journal of Cell Biology
|January 29, 2000
Summary
Homeobox B3 (Hox B3) plays a distinct role in angiogenesis, impacting capillary formation unlike its paralog Hox D3. Restoring ephrin A1 levels rescues impaired blood vessel development, highlighting complementary Hox gene functions.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cell Biology
Background:
- Endothelial cells (EC) utilize Homeobox (Hox) genes for angiogenesis.
- Hox D3 regulates EC adhesion, invasion, and migration via integrin alphavbeta3 and urokinase plasminogen activator (uPA).
Purpose of the Study:
- To investigate the distinct role of the paralogous Hox B3 gene in angiogenesis.
- To elucidate the mechanism by which Hox B3 influences endothelial cell behavior.
Main Methods:
- Using antisense technology to inhibit Hox B3 in cultured dermal microvascular EC.
- Analyzing gene expression, including Hox D3-dependent genes and ephrin A1.
- Supplementing cultures with recombinant ephrin A1/Fc fusion proteins.
- Expressing Hox B3 in the chick chorioallantoic membrane via avian retroviruses to study in vivo angiogenesis.
Main Results:
- Antisense inhibition of Hox B3 impaired capillary morphogenesis in EC.
- Hox B3 inhibition reduced ephrin A1 ligand levels while maintaining Hox D3-dependent genes.
- Recombinant ephrin A1/Fc restored capillary morphogenesis.
- Constitutive Hox B3 expression in vivo increased vascular density and angiogenesis.
Conclusions:
- Hox B3 is required for capillary morphogenesis, distinct from Hox D3's role in EC invasion and migration.
- Hox B3 influences angiogenesis through regulation of ephrin A1.
- Paralogous Hox genes, like Hox B3 and Hox D3, exhibit complementary functions in angiogenesis.