NIH Research Festival
Proper innervation and vascularization are essential in organ development and homeostasis. In embryonic mouse limb skin, sensory nerve-derived chemokine CXCL12 (CXC-motif ligand 12) controls blood vessel branching through its receptor CXCR4 (CXC-motif receptor 4) on endothelial cells, and nerve-derived VEGF-A directs arterial differentiation. This nerve-induced arteriogenesis is followed by sympathetic axon projection. We then sought to understand what happens to sympathetic axon projections to skin targets in the mutants lacking sensory nerve-artery alignments. To address this question, we have developed a novel high-resolution 3D whole-mount imaging of embryonic skin to visualize cellular components and architecture of hair follicles and sweat glands. Our preliminary data have demonstrated that cxcr4 mutants fail to develop arterial branching along with sensory nerves, accompanied by defective sympathetic axon projections in the skin: no sympathetic innervation in large-diameter arteries and sweat glands. We are currently investigating what happens to hair follicle innervation of sympathetic axons. Combined, these data suggest that the process of sympathetic axon projection depends on arterial branching. Furthermore, the defective sympathetic projection to skin targets is a functional consequence of defective sensory nerve-mediated arterial branching in the developing skin.
Scientific Focus Area: Developmental Biology
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