Migration of Cajal-Retzius cells

Cajal-Retzius 细胞的迁移

• 批准号: 6937340
• 负责人: WEI GUAN
• 金额: $ 4.4万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6937340
• 关键词: brain cell; brain morphology; cell migration; cerebral cortex; chemoattractants; developmental neurobiology; genetically modified animals; laboratory mouse; postdoctoral investigator; tissue /cell culture

Lissencephaly (smooth cortex) is caused by abnormal cortical neuronal migration and leads to severe mental retardation and seizures. Cajal-Retzius (CR) cells are early born cortical neurons that have critical functions in regulating the final laminar location of migrating cortical neurons. However, little is known about the developmental program of CR cells. This proposal will investigate the hypothesis that SDF1-CXCR4-mediated chemoattraction and slits-robos-mediated chemorepulsion regulate the migration of cortical hem (CH)-derived CR cells. To test this hypothesis, the CH marker gene Frizzled 10 promoter drived lacz (frz10-lacz) transgenic mice, Frz10-lacz-CXCR4 null mice and Frz10-lacz-slit1/2 null mice will be generated and the migration of CH-derived CR cells in these mice will be analyzed in vitro and in vivo. For in vitro assays, brain slice and CH explant collagen cultures will be stained with lacz antibody to examine whether Frz10-lacz-CXCR4 null mice and Frz10-lacz-slit1/2 null mice show any CR cell migration defects. If so, overexpression experiments with electroporation of SDF1 and slits in vitro and in vivo will be performed. The results from these experiments will provide some insight for developing novel therapeutic targets in Lissencephaly.

Lissphaly（平滑皮层）是由皮质神经元异常引起的，导致严重的智力低下和癫痫发作。 Cajal-Retzius（CR）细胞是早期出生的皮质神经元，在调节迁移皮质神经元的最终层流位置方面具有关键功能。但是，对于CR细胞的发展程序知之甚少。该提议将研究以下假设：SDF1-CXCR4介导的趋化收集和裂隙 - 摩布斯介导的化学乳头调节皮质下摆（CH）衍生的CR细胞的迁移。为了检验这一假设，CH标记基因卷曲了10个启动子Drived Lacz（FRZ10-LACZ）转基因小鼠，FRZ10-LACZ-CXCR4 NULL小鼠和FRZ10-LACZ-SLIT1/2 NULL小鼠将产生并产生。 这些小鼠中Ch衍生的CR细胞的迁移将在体外和体内分析。对于体外测定，将用LACZ抗体染色脑切片和CH Epplant胶原蛋白培养物，以检查FRZ10-LACZ-CXCR4无效小鼠和FRZ10-LACZ-SLIT1/2 NULL小鼠是否显示出任何CR细胞迁移缺陷。如果是这样，将在体外和体内进行SDF1电穿孔和缝隙的过表达实验。这些实验的结果将为开发新的治疗靶标提供一些见识。