Sexy glia: developmental plasticity during glia-derived neurogenesis (360G-Wellcome-207483_Z_17_Z)

The overall goal of this proposal is to elucidate the cellular and molecular mechanisms that regulate natural glia-to-neuron cell-fate switches. Stably differentiated cells can sometimes display a remarkable degree of plasticity and switch fates to another differentiated cell type, in a process termed transdifferentiation. In the vertebrate nervous system, radial glia act as neural progenitors during embryogenesis. Suprisingly, stably differentiated glia can also act as neural progenitors during adult neurogenesis. We have recently discovered two cases in which stably differentiated glial cells undergo a glia-to-neuron cell-fate switch during sexual maturation in the nervous system of C. elegans, allowing us to study these events at the single-cell level in a genetically tractable system. We will combine classic genetic approaches with state-of-the-art molecular and next-generation sequencing approaches to characterise the molecular and epigenetic changes that occur during natural glia-to-neuron transdifferentiation. We will elucidate the role of cell division in this process, identify novel molecular regulators and determine the reprogramming abilities of the factors we identify. Unleashing the neurogenic potential of glia offers tremendous therapeutic possibilities.