Accurate neuronal and vascular growth during development is critical for an organism’s function and survival. Neurons, however, would not grow into a spinal cord, nor would endothelial cells form vascular tissue, if not for molecular guidance signals. These cells are blind to the fate of their growth. Two decades ago, my lab, with numerous collaborators, began the process of elucidating multiple chemotropic proteins expressed in mouse models of the developing nervous system. Their presence selectively attracts and repels axons to guide their growth. These chemotropic factors play dual roles depending on the receptor to which they bind and the interactions between these receptors. In tracking the unique growth pathway of commissural axons, we characterized the activity of five receptor-ligand complexes. We showed neuron attraction was mediated by DCC-Netrin and Rig-1-Slit complexes, and repulsion was mediated by Unc5-Netrin, Robo-Slit, and Neuropilin-Semaphorin complexes. Additionally, we learned that classical morphogens, such as Wnt and Shh, also function as chemoattractants. Most recently, we have found that several of these chemotropic factors, such as Netrin and Semaphorin, play parallel roles in guiding vascular growth. My current research aims to expose the extent of this parallel and apply this knowledge to design therapies promoting neural regeneration after injury, as well as inhibiting tumor angiogenesis.
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