Cell Identity Determination in Cerebral Cortex

大脑皮层细胞身份测定

• 批准号: 7435319
• 负责人: Christopher A. Walsh
• 金额: $ 33.55万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-12-16 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7435319
• 关键词: Address; Adherens Junction; Affect; American; Apical; Biochemical; Brain; Cell Fate Control; Cell Lineage; Cell division; Cells; Centrosome; Cerebral cortex; Cerebrum; Complex; Ensure; Epilepsy; Epithelial; Genes; Goals; Grant; Human; Human Development; Immigration; Inherited; Invertebrates; Learning Disorders; Localized; Mental Retardation; Microcephaly; Mitotic; Mitotic Spindle Apparatus; Mitotic spindle; Mus; Mutant Strains Mice; Mutation; Neuroepithelial Cells; Neuronal Differentiation; Neurons; Object Attachment; Pattern; Proteins; Regulation; Research Personnel; Role; Stem cells; Structure; Testing; Tissues; Work; cognitive function; daughter cell; histogenesis; intracellular protein transport; nervous system disorder; neuroepithelium; neurogenesis; programs; protein expression; protein localization location; protein transport

DESCRIPTION (provided by applicant): Normal development of human cerebral cortex is essential for cognitive function, and is disrupted in many human neurological disorders that are associated with epilepsy, mental retardation, or other learning disorders. The first cycle of this grant used retroviral lineage markers to analyze cell division and neuronal migration in the cerebral cortex. The second cycle of this grant, now ending, continued the cell lineage analysis and examined a few specific genes that regulate cortical patterning and cell fate. These studies have led us to an analysis of the control of the subcellular localization of specific proteins, and studies of their role in controlling cell fate in the developing cerebral cortex. Particular proteins are known to be expressed asymmetrically in dividing cells, and are hence inherited preferentially by one of the two daughter cells of dividing cell. This asymmetric inheritance of protein determinants appears to be an important means of determining cell fate in many species. The first specific aim of this grant proposes to analyze the polarized expression of several protein complexes in developing neuroepithelial cells of the cerebral cortex, in relation to centrosomes. The second specific aim proposes to analyze how these polarized patterns of protein expression influence epithelial polarity and neurogenesis in the cerebral cortex. Finally, the third specific aim analyzes the role of the centrosome in neurogenesis, and the biochemical and functional connection between polarized protein expression and mitotic spindle orientation in the cortical neuroepithelium.

描述（由申请人提供）：人类大脑皮层的正常发育对于认知功能至关重要，并且在许多与癫痫、精神发育迟滞或其他学习障碍相关的人类神经系统疾病中被破坏。这项资助的第一个周期使用逆转录病毒谱系标记来分析大脑皮层中的细胞分裂和神经元迁移。第二个周期的补助金，现在结束，继续细胞谱系分析，并检查了一些特定的基因，调节皮质图案和细胞命运。这些研究使我们分析了特定蛋白质的亚细胞定位控制，并研究了它们在发育中的大脑皮层中控制细胞命运的作用。已知特定蛋白质在分裂细胞中不对称表达，因此优先由分裂细胞的两个子细胞之一遗传。蛋白质决定簇的这种不对称遗传似乎是许多物种中决定细胞命运的重要手段。这项资助的第一个具体目标是分析几种蛋白质复合物在大脑皮层发育中的神经上皮细胞中与中心体相关的极化表达。第二个具体目标是分析这些蛋白质表达的极化模式如何影响大脑皮层的上皮极性和神经发生。最后，第三个具体目标分析了中心体在神经发生中的作用，以及极化蛋白表达和皮质神经上皮细胞有丝分裂纺锤体方向之间的生物化学和功能联系。