Cell Adhesion Molecules in CNS Development

影响中枢神经系统（CNS）的发育缺陷和退行性变化 导致包括痴呆、癫痫、精神分裂症、帕金森氏症和 _，lyngal病。了解调节CNS发育的机制， 功能有望为神经系统疾病的分子发病机制提供见解。 神经元的发育和生理是由它们与邻近神经元的相互作用来调节的。 细胞和细胞外基质（ECM）分子。受体的作用机制 介导这些相互作用调节神经元发育和健康的定义很差。 我们的长期目标是了解细胞与细胞以及细胞与ECM相互作用的机制， 调节CNS的发育、维持和功能。我们在这里建议研究ECM受体 β-整联蛋白家族的一部分。我们假设β-整联蛋白是一种调节性的蛋白质， 在中枢神经系统中控制皮质前体细胞的细胞周期进程的网络。来测试我们 假设，我们将使用携带floxed等位基因，Cre和GFP的转基因小鼠来分析 通过BrdU标记和免疫组化检测细胞增殖和分化缺陷 β 1-缺陷的CNS前体在体内，并在体外流式细胞仪分选后。我们的初步数据 验证我们的假设他们表明β-整联蛋白调节神经源性区域的增殖， 我们预期β 1-整合素是协调细胞周期的调节回路的一部分 通过分化和迁移退出。确定调控这些机制的机制， 事件对于了解CNS发展和疾病进展以及控制 神经干细胞的好处，以便将它们用作治疗剂。

Developmental defects and degenerative changes that affect the central nervous system (CNS) lead to neurological disorders including dementia, epilepsy, schizophrenia, Parkinson's and _,lzheimer's disease. An understanding of the mechanisms that regulate CNS development and Function is expected to provide insights into the molecular pathogenesis of neurological disorders. The development and physiology of neurons is regulated by their interactions with neighbouring cells and with the extracellular matrix (ECM) molecules. The mechanisms by which receptors that mediate these interactions regulate neuronal development and health are poorly defined. Our long term goal is to understand the mechanisms by which cell-cell and celI-ECM interactions regulate CNS development, maintenance, and function. We propose here to study ECM receptors of the betal-integrin family in the CNS. We hypothesis that betal-integrins are part of a regulatory network that controls cell cycle progression of cortical precursor cells in the CNS. To test our hypothesis, we will use genetically modified mice carrying floxed alleles, Cre, and GFP to analyze by BrdU labeling and immunohistochemistry defects in cell proliferation and differentiation of beta1 -deficient CNS precursors in vivo, and after FACS sorting in vitro. Our preliminary data validate our hypothesis. They show that betal-integrins regulate proliferation in neurogenic zones of the CNS.We expect that beta1 -integrins are part of the regulatory circuit that coordinates cell-cycle exit with differentiation and migration. The identification of the mechanisms that regulate these events is important to understand CNS development and disease progression, as well as to control the bevavior of neural stem cells in order to use them as therapeutic agents.