How are developmental processes coordinated to build functional circuitry? (360G-Wellcome-225986_Z_22_Z)

During brain development, the birth, specification, differentiation, and survival of diverse cell types are coordinated to generate circuits spanning neural fields, yet we understand little of how this is achieved. My proposal will address how development is coordinated at multiple levels to build functional circuitry using the well-characterised and tractable Drosophila visual system. Recently, my lab discovered that photoreceptors regulate the neuronal diversity of their target field, the lamina, through a Hedgehog signalling gradient. Unlike other known morphogen gradients, which emanate away from the source, here the gradient forms along the lengths of photoreceptor axons. Aim 1 will determine how photoreceptors establish this unique instructive gradient. While Hedgehog signalling specifies lamina neuron identities, MAPK signalling drives neuronal commitment. Aim 2 will define the downstream molecular mechanisms that underpin and coordinate neuronal specification and commitment. Finally, based on our findings that developmental coordination often relies on intercellular signalling, Aim 3 will systematically survey and validate receptor-ligand pair expression from single cell transcriptomic datasets to uncover novel intercellular communication that coordinates neural development. Achieving these aims and addressing developmental coordination will fill a gaping hole in our understanding of nervous system development, with far-reaching implications for basic biology and medicine.