Proj 1: Neurodevelopment Dyx1c1 and Mechanisms of Neuronal Migration in Neocortex

项目 1：神经发育 Dyx1c1 和新皮质神经元迁移机制

• 批准号: 8914760
• 负责人: Joseph J LoTurco
• 金额: $ 2.96万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8914760
• 关键词: Binding; Biological; Biological Assay; Cell Adhesion; Cell Culture Techniques; Data; Defect; Degradation Pathway; Dependence; Development; Dyslexia; Electroporation; Failure; Functional disorder; Gene Targeting; Genes; Genetic; Growth; Homologous Gene; Image; Immigration; Impairment; Lead; Learning Disabilities; Life; Link; Methods; Molecular; Neocortex; Neurites; Neurobiology; Neuroglia; Neurons; Pathway interactions; Play; Process; Proteins; RNA Interference; Radial; Rattus; Reading Disabilities; Rodent; Role; Staging; Susceptibility Gene; System; Tamoxifen; Testing; Work; axon growth; axon guidance; cellular imaging; chaperonin; functional disability; in utero; in vivo; migration; neocortical; neurodevelopment; neuron development; novel; overexpression; protein degradation; protein protein interaction; research study; ubiquitin ligase

The specific causes of dyslexia are not yet known. Recent genetic and neurobiological studies strengthen a working hypothesis that dyslexia is caused by early developmental disruptions that subsequently cause functional impairments in neocortical circuits. Within the past four years, 4 candidate dyslexia susceptibility genes with roles in neuronal development have been proposed (DYX1C1, KIAA0319, DCDC2 and ROBO1). Rodent homologs of three of these, Dyxld, Kiaa0319 and Dcdc2 have been shown by our group to play a role in neuronal migration in'developing neocortex, and Robol was previously shown to be important for axon growth and guidance. The three aims of this project will further define the cellular and developmental roles of Dyxld. The proposed experiments will define the components of neuronal migration and differentiation regulated by Dyxld, and identify functional links between Dyxld and other proteins essential to migration. The aims will be executed by a combination of in utero RNAi, imaging, protein-protein interaction assays, and cell culture approaches. Novel in vivo conditional RNAi and overexpression methods will be used to explore the temporal dependence of Dyxld function, and potential developmental reversibility of Dyx1c1 dysfunction. Together, these experiments will lead to a comprehensive molecular and cellular understanding of the function of a gene linked to reading and learning disability.

阅读障碍的具体原因尚不清楚。最近的遗传和神经生物学研究加强了