Non-Radial Cell Migration in CNS Development

中枢神经系统发育中的非径向细胞迁移

• 批准号: 7163543
• 负责人: Jeffrey A Golden
• 金额: $ 26.8万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-15 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7163543
• 关键词: Non; Radial; Cell; Migration; CNS

Epilepsy, mental retardation and structural anomalies of the brain often have a genetic etiology. Although they affect 3-5% of all children, the underlying pathogeneses for these disorders is poorly understood in most cases. Cell migration is a central component of normal central nervous system (CNS) development and disruptions in this process have been implicated in the development of multiple disorders such as Fukuyama Muscular dystrophy, Miller-Dieker Syndrome, Walker-Warburg Syndrome, and the Muscle-Eye-Brain syndrome to name just a few. Two primary patterns of cell migration are recognized during CNS development, radial and non-radial. While the cellular and molecular bases of radial cell migration, long considered the predominant mode of cell migration, have begun to be defined, the mechanisms of guidance for non-radial cell migration remain largely unexplored. Using lineage analysis, we have defined the developmental time and location where non-radial cell migration begins in the chick forebrain. Based on these data we have developed a model to explain the cellular and molecular mechanisms of non-radial cell migration. Our model is based on the hypotheses that cell surface molecules, secreted molecules, and extracellular matrix molecules guide non-radially migrating cells. This proposal will begin to address our hypothesis by 1) directly testing several components of our model, and 2) generate a mammalian model to further study one of the molecules we have identified as a component of non-radial cell migration in the chick. These data will certainly enhance our understanding of normal CNS development. Furthermore, we anticipate the data from these studies will provide insight into the pathogenesis of a variety of inherited and non-inherited conditions that afflict children such as epilepsy, mental retardation and structural malformations of the brain. This may ultimately lead to improvements in the diagnosis, management, and prevention of neurological diseases where abnormal cell migration has a pathogenetic role.

癫痫、智力迟钝和大脑结构异常通常有遗传病因。虽然