UNDERSTANDING THE FUNCTION AND SIGNALLING MECHANISMS OF VEGF-A AND VEGF-C IN OPTIC CHIASM DEVELOPMENT.

During development, the billions of nerve cells in our brains and eyes must make appropriate connections with correct target regions. This is achieved by the directed guidance of neuronal processes along highly specific pathways, which are laid down by chemical cues. Mistakes made during axon pathfinding from the eye to the brain, for example as a result of loss of eye pigmentation in albinism, result in an impaired ability to see in depth. Moreover, defects in axon pathfinding within the brain have been linked to the development of disorders such as autism and schizophrenia. Understanding how brain and eye connections form normally may also help devise novel strategies for nerve regeneration following injury or damage to the adult nervous system, for example following optic nerve damage or stroke. Recently, we discovered that a molecule best characterised as a growth factor for blood vessels, which is known as vascular endothelial growth factor (VEGF-A), affects nerve wiring between the eye and brain. Specifically, we found that VEGF-A is essential for the routing of nerve processes that extend from each eye into the opposite brain hemisphere to help us see objects in depth. More recently, we discovered that a related molecule called VEGF-C also affects nerve wiring between the eye and brain. We now seek funding to determine the precise role of VEGF-C in this process, to investigate how VEGF-A and VEGF-C cooperate in establishing the wiring that is necessary for normal vision, and to establish how their signals are transmitted within the nerve cables. This research will advance our understanding of normal brain wiring and, in the future, will likely advance the development of clinical therapies that promote repair and regeneration following damage to the eye and its brain targets.