SURFACE MEDIATED MECHANISMS OF NEURONAL MIGRATION

神经元迁移是一个特殊的事件，它确保了有丝分裂后神经元的迁移。 在胚胎脑室区产生的神经元获得其适当的 在成熟大脑中的位置，并建立其成人表型 身份 在哺乳动物胚胎中，大多数有丝分裂后的神经元， 从大脑皮层到达它们的永久居所， 沿着已被鉴定为 瞬时放射状胶质细胞。 这个项目分析了 这种动态过程的机制，通过关注分子键， 在迁移过程中吸引并粘附神经元到胶质细胞。 使用多克隆 先前制备的放射状神经胶质细胞上抗原的抗体（D4） 本基金的循环和两种新的小鼠单克隆抗体（14 D 7和 19 G11），我们已经证明了两个不同的“微域”的存在。 在桡动脉游离表面上有48 kD和72 kD分子量的抗原 体外培养的胚胎脑壁胶质细胞。 到目前为止， 唯一鉴定的识别分子分离自神经胶质侧， 神经元-神经胶质连接处 在这里，我们建议进一步描述 这些多肽的出现、分布和功能 活胚胎的胚胎脑壁。 为了实现这一挑战， 目标，我们提出了以下逻辑为我们的研究：1）检查 胶质细胞表面微区蛋白的表达和定位 在体内神经元迁移过程中的各个阶段：2）研究 胶质细胞表面抗体对神经元迁移的调节 3）表征神经胶质细胞表面微结构域蛋白， 识别神经元侧的相应受体分子， 微区结 我们有所有必要的方法，人员和 设备以及独特的抗体电池，以确定神经胶质细胞 细胞表面抗原来实现这些目标。 这些研究提供了一个 有机会获得分子机制的全面看法 神经元迁移的关键发展事件的基础，并获得 深入了解各种迁移性疾病的发病机制， 皮质（和皮质下）畸形的基础。

Neuronal migration is an extraordinary event which insures that postmitotic neurons generated in the embryonic ventricular zone acquire their proper positions in the mature brain and establish their adult phenotypic identities. In the mammalian embryo, most postmitotic neurons destined to form the cerebral cortex reach their permanent residences by following along the surface of elongated fibers that have been identified as transient radial glial cells. This project analyzed the molecular mechanisms of this dynamic process by focusing ont he molecular bonds that attract and adhere neurons to glia during migration. Using polyclonal antibodies (D4) to antigens on radial glial cells made in the previous cycle of this grant and two new mouse monoclonal antibodies (14D7 and 19G11), we have demonstrated the presence of two distinct "microdomain" antigens of 48 kD and 72 kD molecular weight on the free surface of radial glial cells in the embryonic cerebral wall in vitro. Up to now, these are the only identified recognition molecules isolated from the glial side of the neuron-glia junction. Here we propose to characterize further the emergence, distribution, and function of these polypeptides in the embryonic cerebral wall of living embryos. To attain this challenging goal, we propose the following logic for our studies: 1) examine expression and localization of the glial cell surface microdomain proteins at various stages during neuronal migration in vivo: 2) study the modulation of neuronal migration by antibodies to glial cell surface microdomains; 3) characterize glial cell surface microdomain proteins and identify the corresponding receptor molecules on the neuronal side of the microdomain junctions. We have all the necessary methods, personnel and equipment as well as a unique battery of antibodies to identified glial cell surface antigens to address these goals. These studies offer an opportunity to obtain a comprehensive view of the molecular mechanisms underlying the critical development event of neuronal migration and to gain insight into the pathogenesis of a variety of migratory disorders that underlie cortical (and subcortical) malformations.