NEUROGENESIS AND MIGRATION IN DEVELOPING CEREBRAL CORTEX

大脑皮层神经元回路的功能是我们 最高的认知和感知能力，然而， 皮层神经元之间特异性连接的形成主要是 未知 在发育过程中，皮层的增殖细胞 神经上皮细胞产生年轻的神经元， 在大脑皮层的不同位置， 进入形成皮层结构基础的层和柱 处理. 大脑皮质的产生和迁移缺陷 神经元对心理健康有着重要的意义， 由于迁移障碍与精神分裂症有关， 躁郁症 本研究的目的是探索 细胞和分子过程， 哺乳动物的大脑皮层产生年轻的神经元， 神经元迁移到脑内的适当位置。 目前正在研究五个具体问题：1）哪些细胞骨架元素 支持细胞周期中的核迁移？我们将 首先描述细胞骨架的基本要素， 细胞内运动，然后测试破坏细胞核的影响， 对细胞进行表型定型能力的影响。2)什么 是产生年轻皮层神经元的细胞分裂模式 我们建议直接成像心室中细胞分裂的模式， 使用延时共聚焦显微镜来确定细胞是否 划分是对称的或不对称的。 3)什么是路径 大脑皮层发育过程中的神经元迁移延时成像 技术将被用来描述迁移的多样性， 在发育中的大脑皮层切片中的通路。 4)有哪些 用于径向和正交方向迁移的细胞基质 （切向）域？ 我们将探索一系列可能的底物， 径向和非自由基迁移，使用电子显微镜， 免疫组织化学技术。 5)需要哪些分子 在径向和正交域的迁移运动？ 我们将 表征放射状神经元迁移的分子基础， 通过使用功能阻断抗体（以 分子如β 1-整合素、L1和NCAM）和延时成像 技术. 这些实验的结果将为我们提供关于 神经发生和神经元分化的细胞和分子机制 大脑皮层的迁移 这些研究正常 发育可能为个体发育提供重要的见解 人类大脑发育障碍，并最终产生 适当治疗这些疾病的策略。

The functioning of neuronal circuits in the cerebral cortex underlies our highest cognitive and perceptual abilities, yet the rules underlying the formation of specific connections among cortical neurons are largely unknown. During development, proliferating cells of the cortical neuroepithelium generate young neurons that migrate away from their site of origin into distinct positions within the cortex, where they assemble into the layers and columns that form the structural basis of cortical processing. Defects in the production and migration of cerebral cortical neurons have fundamental implications for mental health, particularly since migration disorders have been implicated in schizophrenia and bipolar affective illness. The goal of this research is to explore the cellular and molecular processes by which neural progenitor cells in the mammalian cerebral cortex produce young neurons, and to study how these neurons migrate to appropriate positions within the brain. Five specific issues are under study: 1) Which cytoskeletal elements support interkinetic nuclear migration during the cell cycle? We will first characterize the cytoskeletal elements that underlie this intracellular movement, then test the effects of disrupting nuclear movements on the ability of cells to make phenotypic commitments. 2) What are the patterns of cell division that produce young cortical neurons? We propose to image directly patterns of cell division in the ventricular zone using time-lapse confocal microscopy to determine whether cell divisions are symmetric or asymmetric. 3) What are the pathways for neuronal migration in the developing cerebral cortex? Time-lapse imaging techniques will be used to characterize the diversity of migratory pathways in slices through the developing cortex. 4) What are the cellular substrates for migration in the radial and orthogonal (tangential) domains? We will explore a range of possible substrates for both radial and nonradical migration, using electron microscopy and immunohistochemical techniques. 5) What molecules are required for migratory movements in the radial and orthogonal domains? We will characterize the molecular basis of neuronal migration in the radial and orthogonal domains through the use of function-blocking antibodies (to molecules such as Beta1-integrin, L1, and NCAM) and time-lapse imaging techniques. The results of these experiments will provide us with information about the cellular and molecular mechanisms of neurogenesis and neuronal migration in the developing cerebral cortex. Such studies of normal development are likely to provide important insights into the ontogeny of developmental brain disorders in human, and ultimately to generate strategies for the appropriate treatment of such disorders.