David Holcman

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  Modeling neurite outgrowth
  David Holcman

  Neurite growth is a fundamental process of neuronal development, which requires both membrane expansions by exocytosis and cytoskeletal dynamics. However the specific contribution of these processes has not been yet assessed quantitatively. In this talk, I will present a biophysical model in which we relate the overall neurite outgrowth rate to the vesicle dynamics. We considered the complex motion of vesicles in the cell soma and demonstrated from biophysical consideration, that the main step of finding the neurite initiation site relies mainly on a two dimensional diffusion/sequestration/fusion at the cell surface and we obtain a novel formula for the flux of vesicles at the neurite base. In the absence of microtubules, a nascent neurite initiated by vesicular delivery can only reach a small length. By adding the microtubules dynamics to the secretory pathway and using stochastic analysis and simulations, we showed that the complex dynamics of neurite growth depends on the coupling parameter between the microtubules and the neurite.To validate one aspect of our model, we demonstrated that the experimental flux of TI-VAMP but not Synaptobrevin 2 vesicles contributes to the neurite growth. We conclude that although vesicles can be generated randomly in the cell body, the search for the neurite position using the microtubule network and diffusion is quite fast. Finally our study demonstrates that cytoskeletal dynamics is necessary to generate long protrusion, while vesicular delivery alone can only generate small neurite.