Laminin Signaling and Neural Stem Cell Differentiation

描述(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，但它在命运决定中的作用仍然很大程度上是未知的。整合素受体可以内化细胞外基质的信号，导致细胞形态和基因表达的变化，以响应细胞外环境信号。根据本实验室最近观察到的层粘连蛋白的IKVAV序列促进神经干细胞分化和抑制神经干细胞的胶质生成，推测整合素信号在上下文相关的神经干细胞谱系承诺和分化中发挥重要作用。在这项提议中，将通过交替阻断和激活神经干细胞中几个水平的整合素信号并观察由此产生的分化特征来检验这一假说。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，并观察胶质瘢痕形成和轴突萌发的变化，将确定增加的整合素信号在损伤的大鼠脊髓中阻止胶质生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.