Laminin Signaling and Neural Stem Cell Differentiation

描述（由申请人提供）：尽管细胞外基质（ECM）是一个富含结构和信号分子的环境，但其在命运规范中的作用仍在很大程度上未知。整合素受体可以内化来自ECM的信号，导致细胞形态和基因表达的变化，以响应细胞外环境信号。根据本实验室最近的观察，层粘连蛋白的IKVAV序列促进神经干细胞的神经元分化和抑制胶质瘤的发生，假设整合素信号在上下文依赖的神经干细胞谱系承诺和分化中起重要作用。在本研究中，我们将通过在神经干细胞的多个水平上交替阻断和激活整合素信号，并观察由此产生的分化情况，来验证这一假设。通过注射一种含有IKVAV层粘连蛋白序列的新型纳米工程凝胶，观察胶质瘢痕形成和轴突发芽的变化，可以确定整合素信号传导增加阻断损伤大鼠脊髓胶质形成和促进再生的能力。

DESCRIPTION (provided by applicant): 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.