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: 7915803
• 负责人: Jeffrey A Golden
• 金额: $ 37.01万
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7915803
• 关键词: Affect; Autistic Disorder; Biological; Biological Assay; Brain; Cell Migration Pathway; Cells; Cerebral cortex; Cerebrum; Child; Childhood; Complex; Cortical Malformation; Cues; Cytoskeleton; Data; Defect; Development; Diagnosis; Disease; Dynein ATPase; Environment; Epilepsy; Exhibits; Functional disorder; Generations; Grant; Growth Cones; Healthcare; Human; In Vitro; Interneurons; Lead; Length; Link; Logic; Mammals; Mental Retardation; Microtubule Stabilization; Microtubules; Molecular; Mus; Mutant Strains Mice; Mutation; Neuraxis; Neuronal Migration Disorder; Neurons; Nuclear; Outcome; Pathogenesis; Pathway interactions; Patients; Pattern; Population; Prevention; Process; Publishing; Radial; Retinal Cone; Rodent; Role; Signal Transduction; Slice; Testing; Travel; Tubulin; United States; Ventricular; Work; axon guidance; base; cell motility; extracellular; in vivo; insight; lissencephaly; migration; mutant; nervous system development; nervous system disorder; response

Cell migration is fundamental to normal central nervous system (CNS) development and perturbations in this process have been implicated in the pathogenesis of many neurologic disorders including epilepsy, mental retardation and autism. Understanding the pathogenesis of these all to common disorders requires, among other processes, the elucidation of the molecular and cellular mechanisms governing neuronal migration. Two primary pathways of cell migration are recognized during cerebral cortical development, radial and non-radial. At least in rodents, radial cell migration, from the pallial ventricular zone out to the cortical plate, gives rise to the projection neurons of the cerebral cortex, whereas cortical interneurons must travel along non-radial pathways from the subpallial proliferative zones to arrive in the cortical plate. Over the past five years, supported by this grant, we have made significant contributions to our understanding of interneuron migration. Over the next two years we plan to extend these studies to more clearly define the mechanisms governing non-radial cell migration in mammals. One fundamental questions is how does the leading process respond to guidance cues to direct the migrating interneurons from the ganglionic eminence along their circuitous path and finally into the cerebral cortex. We have hypothesis that the leading process functions like a growth cone by dynamically regulating its cytoskeleton in response to long and shortrange cues. Herein we propose to define the cytoskeletal dynamics in the migrating leading processes and establish how they are regulated by guidance cues (aim 1) and determine how Lis1 effects leading process dynamics (aim 2). Together these data will establish the cellular mechanisms by which the leading process is able to lead the migrating interneuron, an integral component of normal brain development and one that is disrupted in many neurologic disorders.

细胞迁移是正常中枢神经系统（CNS）发育的基础，并且在此过程中的扰动已经涉及许多神经系统疾病（包括癫痫、精神发育迟滞和自闭症）的发病机制。了解这些常见疾病的发病机制，除其他过程外，需要阐明神经元迁移的分子和细胞机制。在大脑皮层发育过程中，细胞迁移的两个主要途径是放射状和非放射状。至少在啮齿类动物中，放射状细胞迁移，从苍白球脑室区到皮质板，产生大脑皮质的投射神经元，而皮质中间神经元必须沿着沿着非放射状通路从苍白球下增殖区到达皮质板。在过去的五年里，在这笔赠款的支持下，我们对我们对interneuron迁移的理解做出了重大贡献。在接下来的两年里，我们计划扩展这些研究，以更清楚地定义哺乳动物非放射状细胞迁移的机制。一个基本的问题是，引导过程如何响应引导线索，引导迁移的中间神经元从神经节隆起沿着迂回的路径，最终进入大脑皮层。我们有一个假设，即引导过程的功能就像一个生长锥，通过动态调节其细胞骨架响应长和短距离线索。在这里，我们建议定义的细胞骨架的动态迁移的领导过程中，并建立它们是如何调节的指导线索（目的1），并确定如何Lis1的影响领导过程的动态（目的2）。这些数据将共同建立细胞机制，引导过程能够引导迁移的中间神经元，这是正常大脑发育的一个组成部分，在许多神经系统疾病中被破坏。

项目成果

XLMR candidate mouse gene, Zcchc12 (Sizn1) is a novel marker of Cajal-Retzius cells.

• DOI: 10.1016/j.gep.2010.12.005
• 发表时间: 2011-03
• 期刊: Gene expression patterns : GEP
• 作者: Cho G;Lim Y;Golden JA
• 通讯作者: Golden JA

Lis1 reduction causes tangential migratory errors in mouse spinal cord.

Lis1 减少会导致小鼠脊髓发生切向迁移错误。

• DOI: 10.1002/cne.22768
• 发表时间: 2012
• 期刊: The Journal of comparative neurology
• 作者: Moore,KatherineD;Chen,Renee;Cilluffo,Marianne;Golden,JeffreyA;Phelps,PatriciaE
• 通讯作者: Phelps,PatriciaE