液-液相分離によるニューロンの無中心体性微小管核形成

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Our previous studies emphasize a critical role for local amplification of microtubule generation pathways in differentiating neurons. Microtubule generation is also amplified in response to synaptic activity, and to neuron injury, where it plays a role in neuroprotection and regeneration. This raises the question of what molecular mechanisms underlie this amplification. In this project we looked for a new non-canonical process of microtubule generation in neurons; I have screened through unstudied proteins important for arbor development that act by driving postmitotic microtubule nucleation. Live imaging of microtubule nucleation activity (in vivo EB1 imaging), identifying a new factor required for this process. By manipulation of this factor I show that Drosophila c4da sensory neurons exhibit a dramatic reduction in microtubule nucleation at dendrite tips, with a significant modification in anterograde microtubule numbers. This reduction in microtubule nucleation is apparent across the entire microtubule arbor but is preferentially reduced at the dendrite tips. Live imaging of c4da neuron growth reveal that c4da neurons exhibit reduced arbor extension rate, and reduced branching frequency, leading to a stunted dendritic arbor. I have further investigated the activity of this protein in vitro, finding that it upregulates microtubule nucleation activity.