Cell-Autonomous Control of Neuronal Dendrite Expansion via the Fatty Acid Synthesis Regulator SREBP

Summary: During differentiation, neurons require a high lipid supply for membrane formation as they elaborate complex dendritic morphologies. While glia-derived lipids support neuronal growth during development, the importance of cell-autonomous lipid production for dendrite formation has been unclear. Using Drosophila larva dendritic arborization (da) neurons, we show that dendrite expansion relies on cell-autonomous fatty acid production. The nociceptive class four (CIV) da neurons form particularly large space-filling dendrites. We show that dendrite formation in these CIVda neurons additionally requires functional sterol regulatory element binding protein (SREBP), a crucial regulator of fatty acid production. The dendrite simplification in srebp mutant CIVda neurons is accompanied by hypersensitivity of srebp mutant larvae to noxious stimuli. Taken together, our work reveals that cell-autonomous fatty acid production is required for proper dendritic development and establishes the role of SREBP in complex neurons for dendrite elaboration and function. : Ziegler et al. highlight the endogenous role of fatty acid synthesis for proper neuronal dendrite growth during development. Using Drosophila da neurons, they show that large CIVda neurons cell-autonomously rely on fatty acid synthesis through the lipid synthesis master regulator SREBP. Keywords: Drosophila, dendrite differentiation, fatty acids, lipids, SREBP, metabolism, brain, nociception