Intermediate neuronal progenitors in neocortical development

新皮质发育中的中间神经元祖细胞

• 批准号: 9103235
• 负责人: Robert F Hevner
• 金额: $ 42.44万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9103235
• 关键词: Activity Cycles; Adopted; Affect; Age; Alleles; Area; Autistic Disorder; Cell Cycle; Cerebral cortex; Conscious; Daughter; Defect; Development; Diagnosis; Disease; Embryo; Epilepsy; Evolution; Fibroblast Growth Factor; Fibroblast Growth Factor Receptors; Foundations; Genetic; Goals; Health; Intellectual functioning disability; Knowledge; Label; Language; Measures; Mediating; Mental disorders; Molecular; Molecular Profiling; Motor; Mus; Names; Neocortex; Neurodevelopmental Disorder; Neurons; Play; Preventive treatment; Process; Property; Radial; Receptor Signaling; Regulation; Reporter; Role; Sensory; Signal Transduction; Specific qualifier value; Stem cells; System; Tracer; Ventricular; cell type; cognitive function; cohort; defined contribution; developmental disease; in vivo; mutant; neocortical; nerve stem cell; nervous system disorder; neurogenesis; novel; progenitor; transcription factor; transcriptome

DESCRIPTION (provided by applicant): Intermediate neurogenic progenitors (INPs) are a relatively "new" type of neocortical progenitor cells whose properties, daughter neuron fates, and functions in the regulation of neurogenesis remain unclear. This project will characterize molecular and cellular properties of INPs, define their contribution to cortical areas and layers, and study the regulation of INPs by intrinsic and extrinsic factors. The central hypothesis of this project is that INPs regulate not only overall neurogenesis, but also more subtle aspects of neuron differentiation such as regional identity and laminar fate. These studies will be accomplished using a variety of mouse alleles, including a novel genetic lineage tracing system to identify cortical neurons derived from INP cohorts. The first Aim of this project is to characterize the INP transcriptome, and define proliferative and clonal properties of INPs. The second Aim is to determine the contribution of INP daughter neurons to cortical areas, layers, and cell types. The third Aim is to determine how Eomes, a transcription factor that is specifically expressed in INPs, regulates molecular and developmental properties of INPs. The fourth Aim is to determine how fibroblast growth factor signaling affects INP proliferation and differentiation. Together, these focused studies will provide a coherent understanding of INPs, their roles in corticogenesis, and their possible contributions to neurodevelopmental disorders and therapies. Ultimately, our understanding of diseases such as autism and intellectual disability will be advanced, as will our ability to better diagnose and treat these disorders.

描述(申请人提供)：中间神经源性前体细胞(INPs)是一种相对“新的”类型的新皮质前体细胞，其性质、子代神经元命运和在神经发生调控中的功能尚不清楚。本项目将表征INPs的分子和细胞特性，确定它们对皮质区域和皮层的贡献，并研究内在和外在因素对INPs的调节。这一点的中心假设是 项目是，INP不仅调节整个神经发生，而且还调节神经元分化的更微妙的方面，如区域身份和板层命运。这些研究将使用各种小鼠等位基因来完成，包括一种新的遗传谱系追踪系统，以识别来自INP队列的皮质神经元。本项目的第一个目标是确定INP转录组的特征，并确定INP的增殖和克隆特性。第二个目的是确定INP子代神经元对皮质区域、层和细胞类型的贡献。第三个目的是确定在INP中特异表达的转录因子Eome如何调节INP的分子和发育特性。第四个目的是确定成纤维细胞生长因子信号如何影响INP的增殖和分化。总之，这些重点研究将提供对INP的一致理解，它们在皮质生成中的作用，以及它们对神经发育障碍和治疗的可能贡献。最终，我们对自闭症和智力残疾等疾病的理解将得到提升，我们更好地诊断和治疗这些疾病的能力也将得到提升。