Laminin Signaling and Neural Stem Cell Differentiation

描述（由申请人提供）：尽管细胞外基质（ECM）是一种富含结构和信号分子的环境，但其在命运特化中的作用在很大程度上仍然未知。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响应于细胞外环境线索的变化。本实验室最近观察到层粘连蛋白的IKVAV序列促进神经干细胞中的神经元分化并抑制胶质细胞生成，因此假设整合素信号传导在背景依赖性神经干细胞谱系定型和分化中起重要作用。在这个提议中，这一假设将通过在神经干细胞的几个水平上交替阻断和激活整合素信号传导并观察所得的分化概况来进行测试。通过注射含有IKVAV层粘连蛋白序列的新型纳米工程化凝胶并观察胶质瘢痕形成和轴突发芽的变化，将确定增加的整合素信号传导阻断受损大鼠脊髓中胶质细胞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.