LAMININ AND FIBRONECTIN

本RCDA提案的长期研究目标是了解 细胞外基质（ECM）分子在周围神经 系统（PNS）开发。ECM分子调节细胞的形状、运动和 胚胎发生过程中的分化，以及粘附糖蛋白 纤维连接蛋白（FN）和层粘连蛋白（LAM）在空间和时间上定位于 调节神经嵴分化和神经纤维 伸长率三个具体目标确定了解决这一问题的方法。 首先，FN和LAM的细胞结合结构域与 细胞与完整分子的相互作用组织培养研究将 探针1）粘附在细胞与每个结构域相互作用中的作用，2） 活细胞与特定结构域相互作用时的行为，以及3） 这些相互作用的细胞骨架相关物。第二，FN和LAM 在PNS的发育过程中细胞所使用的方法将是 免疫细胞化学在光镜和电镜水平， 体外分析细胞与复杂基质的相互作用，以及 干扰体内细胞-ECM相互作用。第三，有哪些作用 FN和LAM的特定区域在细胞迁移和分化中的作用 神经嵴细胞 在RCDA的资助下，P.I.将延伸到神经嵴 差异，但学到的技术将适用于研究 神经元行为。将有更长的时间用于 10伦敦国王学院杰奎尼·布罗克斯博士的实验室进行研究 重组DNA的方法来区分亚群的 胚胎和再生细胞，2）神经科学研究所， 俄勒冈州大学（尤金）的几个实验室正在研究神经 系统开发在斑马鱼使用广泛的技术（例如， 分子生物学，活体动物细胞的激光消融，单克隆 抗体产生）。 随着时间的推移，从教学和委员会的责任，PI。 也将能够寻求更有效的研究机会， 新墨西哥州大学。特别是，特殊的图像分析 将利用联合国的设施。这一次也将允许P.I. 开发一门发育神经生物学的研究生课程， 吸引学生到这个研究领域的意图。

The long-range research goal of this RCDA proposal is to understand the roles of extracellular matrix (ECM) molecules in peripheral nervous system (PNS) development. ECM molecules regulate cell shape, movement and differentiation during embryogenesis, and the adhesive glycoproteins fibronectin (FN) and laminin (LAM) are located spatially and temporally to mediate aspects of neural crest differentiation and nerve fiber elongation. Three Specific Aims define approaches to this question. First, what is the relevance of the cell binding domains of FN and LAM to cell interaction with the intact molecule? Tissue culture studies will probe 1) roles of adhesion in cell interaction with each domain, 2) behavior of living cells as they interact with specific domains, and 3) cytoskeletal correlates of these interactions. Second, how are FN and LAM used by cells in the developing PNS? Approaches will be immunocytochemistry at the light and electron microscopic levels, analysis of cell interaction with complex matrices in vitro, and perturbation of cell-ECM interactions in vivo. Third, what are the roles of defined regions of FN and LAM in migration and differentiation of neural crest cells? With RCDA funding, the P.I. will extend approaches to neural crest differentiation, but the techniques learned will be applicable to studies of neuronal behavior as well. Extended periods of time will be spent in 10 the lab of Dr. Jeremey Brockes, Kings College London, to study recombinant DNA approaches to differentiation of subpopulations of embryonic and regenerating cells, and 2) the Neuroscience Institute at the Univ. of Oregon (Eugene) where several labs are studying nervous system development in zebrafish using a wide range of techniques (eg. molecular biology, lasar ablation of cells in living animals, monoclonal antibody production). With time release from teaching and committee responsibilities, the P.I. also will be able to pursue more effectively research opportunities at the Univ. of New Mexico. In particular, the exceptional image analysis facilities at UNM will be exploited. This time will also permit the P.I. to develop a graduate course in developmental neurobiology, with the intention of attracting students to this area of research.