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 在胚胎脑室区域产生的神经元获得其适当的 在成熟的大脑中的位置，并建立他们的成年表型 身份。在哺乳动物胚胎中，大多数有丝分裂后神经元注定要 从大脑皮层通过以下方式到达它们的永久居住地 沿着细长纤维的表面，已被鉴定为 一过性放射状胶质细胞。这个项目分析了分子 这一动态过程的机制主要集中在分子键上 在迁移过程中吸引神经元并将其附着在神经胶质细胞上。使用多克隆 在过去的一年中制造的针对放射状胶质细胞抗原的抗体(D4) 这笔赠款的周期和两个新的小鼠单克隆抗体(14D7和 19G11)，我们已经证明了两个不同的“微域”的存在 辐射自由表面48kD和72kD分子量的抗原 体外培养胚胎脑壁内的神经胶质细胞。到目前为止，这些是 唯一被识别的识别分子是从神经胶质细胞一侧分离出来的 神经元-神经胶质细胞连接。在这里，我们建议进一步描述 这些多肽在体内的出现、分布和功能 活体胚胎的胚胎脑壁。要实现这一挑战 目标，我们为我们的研究提出以下逻辑：1)检查 胶质细胞表面微域蛋白的表达和定位 在体内神经元迁移的不同阶段：2)研究 神经胶质细胞表面抗体对神经元迁移的调节作用 微域；3)表征胶质细胞表面微域蛋白和 确定相应的受体分子在神经元一侧的 微域结。我们有所有必要的方法、人员和 设备以及一组独特的针对已识别的胶质细胞的抗体 细胞表面抗原来解决这些目标。这些研究提供了一个 获得对分子机制的全面了解的机会 神经元迁移的关键发育事件和获得 洞察各种迁徙障碍的发病机制 位于皮质(和皮质下)畸形之下。

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.