Development of venous vascularute system in developing skin

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NHLBI	DEV-5

Authors

• W Li
• Y Mukoyama

Abstract

Blood vessels form a highly branched hierarchical vascular tree composed of arteries and veins during angiogenesis. Recent studies including us have demonstrated that VEGF-A and Notch signaling directs arterial differentiation. However, little is known about what controls venous development, due to lack of definitive molecular markers for venous endothelial cells. We found that EphB1, a EphB class receptor, is specifically expressed by venous endothelial cells, but not arterial and lymphatic endothelial cells, in embryonic and adult skin vasculature models. Interestingly, our extensive analysis of EphB1 expression in developing skin reveals that EphB1 is uniformly expressed in the primitive capillary network at embryonic day 13.5, a stage when no or less arterial markers such as ephrinB2 and Nrp1 are expressed. This observation prompted us to examine whether venous identity may be a default state in early vascular development and whether such venous endothelial cells change their fate in response to VEGF-A and Notch. Indeed, VEGF-A and Notch ligand induce arterial marker expression and in turn suppress venous marker expression in FACS-isolated venous endothelial cells. Ongoing studies to further characterize EphB1+ venous endothelial cells at different embryonic stage would provide insights in understanding mechanisms of venous fate determination and branching pattern.

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