Intermediate neuronal progenitors in neocortical development

新皮质发育中的中间神经元祖细胞

• 批准号: 8720087
• 负责人: Robert F Hevner
• 金额: $ 42.01万
• 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/8720087
• 关键词: Activity Cycles; Adopted; Affect; Age; Alleles; Area; Autistic Disorder; Cell Cycle; Cerebral cortex; Color; Conscious; Daughter; Defect; Development; Diagnosis; Disease; Embryo; Epilepsy; Evolution; Fibroblast Growth Factor; Fibroblast Growth Factor Receptors; Foundations; Gene Expression Profile; Genetic; Goals; Intellectual functioning disability; Knowledge; Label; Language; Measures; Mediating; Mental disorders; Mitosis; Molecular; Molecular Profiling; Motor; Mus; Names; Neocortex; Neurodevelopmental Disorder; Neurons; Play; Process; Property; Radial; Receptor Signaling; Regulation; Reporter; Role; Sensory; Signal Transduction; Specific qualifier value; Staging; 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; public health relevance; transcription factor

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（由申请人提供）：中间神经发生祖细胞（INP）是一种相对“新”类型的新皮质祖细胞，其特性、子神经元命运以及在神经发生调节中的功能仍不清楚。该项目将表征 INP 的分子和细胞特性，定义它们对皮质区域和皮质层的贡献，并研究内在和外在因素对 INP 的调节。这个假设的中心假设 该项目的目的是，INP 不仅调节整体神经发生，还调节神经元分化的更微妙的方面，例如区域身份和层状命运。这些研究将使用多种小鼠等位基因来完成，包括一种新的遗传谱系追踪系统，用于识别源自 INP 群体的皮层神经元。该项目的第一个目标是表征 INP 转录组，并定义 INP 的增殖和克隆特性。第二个目标是确定 INP 子神经元对皮质区域、层和细胞类型的贡献。第三个目标是确定 Eomes（一种在 INP 中特异性表达的转录因子）如何调节 INP 的分子和发育特性。第四个目标是确定成纤维细胞生长因子信号传导如何影响 INP 增殖和分化。总之，这些重点研究将为 INP、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提供一个连贯的理解。最终，我们对自闭症和智力障碍等疾病的理解将得到提高，我们更好地诊断和治疗这些疾病的能力也将得到提高。