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Endothelial cell specification begins just before neural crest cells delaminate from the neural tube and begin their migration into the regions of the branchial arches and head. Thus, neural crest cells come in close physical contact with endothelial cells during their early development. A number of recent studies have demonstrated that endothelial signaling plays a role in organ specification and in neurogenesis, but a role in neural crest development and differentiation has not been evaluated. Using a mouse model with an ENU-induced mutation of VEGFR2, we have shown that development of the cranial ganglia and sensory neuron differentiation from the neural crest is specifically disrupted when the vasculature does not form. We are testing the hypothesis that neurotrophins secreted by endothelial cells regulate neurogenic differentiation of the neural crest and evaluating other pathways of crosstalk between endothelial cells and neural crest.
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