What are the specific cell- cell adhesion related or cytoskeletal mechanisms that determine how neurons migrate, coalesce, and differentiate into distinct layers in the developing cerebral cortex?
Although the significance of cytoskeletal dynamics during the neuronal proliferation and migration is well established, the question of how the dynamic regulation of neuronal cytoskeleton modulates the terminal phase of neuronal migration and leads to the final placement and differentiation of neurons in cortex remains unknown. To explore the significance of cytoskeletal dynamics during this process, we sought to identify and study regulators of the organization and activity of neuronal cytoskeleton in the developing cerebral cortex. To identify such process-specific genes we looked for murine orthologues of Drosophila or C. elegans genes that are known to regulate distinct aspects of neuronal cell migration. Through this screen, we found that Nck associating protein 1 (Nap1), an adaptor protein that activates actin nucleation, is selectively expressed in the cortical plate region of the developing cortex, where neurons terminate their migration and start their final laminar specific differentiation. We are currently investigating how Nap1-mediated cytoskeletal rearrangements in the emerging cortical plate play an essential role in neuronal differentiation underlying the formation of functional connectivity in cerebral cortex..
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