Inactivation of microtubule organizing center function of the centrosome is required for neuronal development and...

Cell differentiation is marked by a dramatic reorganization of the microtubule cytoskeleton that enables diverse cell functions. Mitotic precursor cells arrange microtubules around centrosomes, which become activated as microtubule-organizing centers (MTOCs) through the recruitment of pericentriolar material (PCM) and microtubules to build the mitotic spindle. A hallmark of differentiation is the "inactivation" of centrosomal MTOC function through the loss of PCM and microtubules, yet the function of this inactivation is unknown. We developed a GFP-nanobody-based targeting tool to activate centrosomes in C. elegans differentiated cells. Ectopically activating centrosomes in sensory neurons perturbed microtubule polarity, dynein-mediated trafficking, and caused defects in cell morphology and dendrite pathfinding. Ectopic PCM perturbed ciliogenesis and also protected centrioles from elimination, another common feature of differentiation. By forcing centrosome activation in a fully differentiated cell in a developing organism, we show that centrosome inactivation is required for differentiation by directly contributing to cell form and function.