Although the extracellular matrix (ECM) is an environment rich in structural and signaling molecules, its role in fate specification is still largely unknown. Integrin receptors can internalize signals from the ECM leading to changes in cellular morphology and gene expression in response to extracellular environmental cues. Following the recent observation by this lab that the IKVAV sequence of laminin promotes neuronal differentiation and suppresses gliogenesis in neural stem cells, it is hypothesized that integrin signaling plays an important role in context-dependent neural stem cell lineage commitment and differentiation. In this proposal, this hypothesis will be tested by alternately blocking and activating integrin signaling at several levels in neural stem cells and observing the resulting differentiation profile. The ability of increased integrin signaling to block gliogenesis and promote regeneration in the injured rat spinal cord will be determined by injecting a novel nanoengineered gel containing this IKVAV laminin sequence and observing changes in glial scar formation and axonal sprouting.
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