How do hypoxia-responsive factors such as CXCL12, VEGF-A and EPO regulate the vascular branching morphogenesis during neuro-vascular wiring formation?

Monday, September 22, 2014 — Poster Session I
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NHLBI	DEVBIO-5

Authors

• W Li
• Y Mukouyama

Abstract

During angiogenesis, a primary capillary network undergoes intensive vascular remodeling and develops into a hierarchical vascular branching network. We have shown that peripheral sensory nerves coordinate vascular branching pattern and arterial differentiation during the vascular remodeling. We then seek to understand what environmental signals ensure the nerve-mediated arterial branching. Studies have revealed that hypoxia-induced genes are important regulators of angiogenesis, although the precise mechanism by which they coordinate vascular branching and differentiation remain unclear. We have recently shown that hypoxia-responsive angiogenic factors CXCL12 and VEGF-A coordinate nerve-vessel alignment and arterial differentiation. Furthermore, erythrocyte distribution in a capillary network is in close proximity to the nerves prior to establishment of the nerve-vessel alignment, possibly resulting from erythropoietin (EPO) expression in migrating glial cells in the nerves. Given that CXCL12, VEGF-A and EPO are hypoxia-induced genes and the existence of localized hypoxia prior to nerve-vessel alignment, we have applied multiple approaches to examine whether localized hypoxia functions as an environmental signal to trigger these genes’ expression in the peripheral nerves, thus directing arterial patterning. These experiments have opened up new areas of research into the regulation of branching morphogenesis and patterning by the metabolic microenvironment.

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