Cell Interaction-Dependent Neural Development

中枢神经系统（CNS）由两个主要且不同的细胞群组成：神经元和神经胶质。在许多方面，神经元和神经胶质是专门执行不同的，但互补的任务。事实上，目前认为神经系统的“功能单位”是神经元和与之相关的神经胶质细胞。虽然成熟中枢神经系统的神经元和神经胶质在功能和结构上是不同的，但这两种细胞类型在神经发育过程中来自共同的祖细胞。胚胎发生过程中控制细胞分化的细胞分子机制是本研究的重点。具体来说，Linser博士的实验室已经确定了一种独特的细胞表面糖蛋白，它参与了眼睛视网膜祖细胞分化为神经胶质细胞的最终决定。在目前的项目中，他们将研究这种被称为5A11抗原的细胞表面蛋白如何影响神经胶质细胞表型成熟。分析将包括使用工程逆转录病毒载体引入遗传标记，以及改变5A11基因的表达。由于神经元和神经胶质细胞的分化似乎与细胞何时停止分裂有关，因此该项目将重点放在细胞分化事件上，而不是“终端”或最后的细胞分裂。此外，本研究将比较和对比5A11抗原与两种已知的细胞识别分子，整合素和n -钙粘蛋白的作用。所使用的技术方法主要依赖于当前最先进的分子生物学、生物化学、组织培养和免疫组织化学。提出的研究旨在阐明为神经胶质细胞分化提供驱动力的基本细胞-细胞识别过程。由于神经元和神经胶质彼此如此不同，但却有一个共同的细胞起源，了解产生这些不同细胞类型的机制也将有助于深入了解细胞分化的基本过程。

ABSTRACT 9723874 LINSER The central nervous system (CNS) is composed of two major and distinct populations of cells: neurons and neuroglia. In many ways, neurons and neuroglia are specialized to perform distinct although complementary tasks. Indeed, it is currently believed that the "functional unit" of the nervous system is a neuron and its obligatory associated neuroglia. Although the neurons and neuroglia of the mature CNS are functionally and structurally distinct, both cell types come from common progenitor cells during neural development. The cellular and molecular mechanisms that control cell differentiation during embryogenesis are the focus this research. Specifically, Dr. Linser's laboratory has identified a unique cell-surface glycoprotein that is involved in the final decision of progenitor cells in the retina of the eye to differentiate as neuroglial cells. In the current project, they will investigate how this cell-surface protein, called the 5A11 antigen, influences glial cell phenotype maturation. The analyses will include the use of engineered retroviral vectors to introduce genetic markers as well as to bring about changes in expression of the 5A11 gene. As neuronal and glial cell differentiation seems to be tied to when a cell stops dividing, the project has an overriding focus on the events of cell differentiation relative to "terminal" or the last cell division. In addition, this study will compare and contrast the role of the 5A11 antigen with that of two, well characterized cell-cell recognition molecules, integrin and N-cadherin. The technical approaches to be used rely heavily on current state-of-the-art molecular biology, biochemistry, tissue culture and immunohistochemistry. The proposed studies are designed to shed light on the fundamental cell-cell recognition processes that provide the driving force for neuroglial cell differentiation. Since neurons and neuroglia are so different from one another and yet share a common cell of origin, underst anding the mechanisms that give rise to these different cell types will also provide insight into the fundamental processes of cell differentiation.