Defining the role of VEGF-A signalling in glia during development and in regeneration

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Glial cells nourish and support the information-transmitting neuronal cells of the central nervous system (brain and spinal cord) and the peripheral nervous system (ganglia and nerves). Whilst healthy glia promotes neuronal function, unhealthy glia causes diseases such as multiple sclerosis, diabetic neuropathy and Charcot-Marie-Tooth-Disease. Our pilot experiments suggest that the protein Vascular Endothelial Growth Factor (VEGF) is important for two glial cell types named boundary cap cells and Schwann cells. Boundary caps cells help nerve fibres to cross between the central and peripheral nervous system during development, if therapies were identified that could regenerate boundary caps from their stem cell-like precursors, we could help nerve fibres that re-grow in adults after injury to extend back into the central nervous system. Schwann cells form wrap myelin sheets around nerve fibres to insulate them against each other electrically, and they also help nerve fibres re-grow after injury. Importantly, new Schwann cells can also be generated from boundary cap precursors. We want to find out how VEGF instructs boundary cap and Schwann cells to grow and position themselves in appropriate places during development and disease, in order to identify new molecular targets for medical therapies that promote nerve repair and halt neurodegeneration.