Defining the role of vascular endothelial growth factor (VEGF-A) in commissural axon guidance at the optic chiasm (360G-Wellcome-085476_B_08_Z)

The co-ordinated patterning of nerves and blood vessels is essential for normal physiological function. This functional integration has its basis in development, but the mechanisms that control the co-patterning of nerves and vessels remain poorly understood. The overarching aim of this proposal is to elucidate the contribution of the archetypical angiogenesis factor vascular endothelial growth factor (VEGF-A) and blood vessels to axon guidance in the central nervous system. Our pilot data p rovides convincing evidence that the VEGF-A isoform VEGF164 and its receptor neuropilin 1 (NRP1) play an essential role in retinal ganglion cell (RGC) axon pathfinding at the optic chiasm, where RGC axons decussate to set up the binocular visual pathways. These findings provide the first evidence for a role of VEGF-A in axon guidance in vivo and identify a classical vascular growth factor as a major player in the establishment of contralateral visual projections. We now wish to extend these fi ndings to establish the precise role of VEGF-A at the optic chiasm. In particular, we wish to determine if VEGF-A acts directly on the growth cones of RGC axons or if physical interactions between nerves and blood vessels underlie the role of VEGF-A in axon guidance.