Heterogeneity of Forebrain Neural Precursors

前脑神经前体的异质性

• 批准号: 9054259
• 负责人: Tarik F Haydar
• 金额: $ 68.7万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9054259
• 关键词: Apical; Autistic Disorder; Bioinformatics; Biological; Boston; Brain; Candidate Disease Gene; Cell Cycle; Cell Lineage; Cell Separation; Cells; Cerebral cortex; Classification; Development; Down Syndrome; Embryo; Engineering; Epilepsy; Fingerprint; Gene Expression; Gene Expression Profile; Gene Targeting; Generations; Genes; Genetic; Goals; Growth; Heterogeneity; Individual; Label; Lead; Location; Longitudinal Studies; Mammals; Maps; Measures; Methods; Microfluidics; Mitosis; Mitotic; Mitotic spindle; Molecular; Molecular Profiling; Morphology; Mus; Neocortex; Neuraxis; Neuroglia; Neurons; Output; Population; Positioning Attribute; Production; Prosencephalon; RNA Sequences; Radial; Relative (related person); Resolution; Role; Series; Sorting - Cell Movement; Stem cells; Testing; Time; Universities; Validation; Ventricular; Wild Type Mouse; base; cell type; developmental disease; developmental neurobiology; differential expression; excitatory neuron; fetal; gray matter; hippocampal pyramidal neuron; in vivo; loss of function; neocortical; nerve stem cell; neural precursor cell; neurogenesis; neurogenetics; next generation; novel; offspring; precursor cell; prenatal; protein expression; public health relevance; research study; tool; transcriptome sequencing; transcriptomics

 DESCRIPTION (provided by applicant): Two major goals of developmental neurobiology are to identify the germinal cells which form the central nervous system and to characterize the cellular and molecular mechanisms by which these cells generate the proper numbers and types of neurons. This proposal represents our ongoing efforts to precisely define the molecular and morphological identity of each neural precursor type present in the mammalian neocortical wall. In this project, the Haydar lab at Boston University teams with the Sestan lab at Yale University to perform genetic fate mapping of precursor populations, followed by next generation RNA sequencing at both the bulk and single cell level. Several differentially expressed genes have already been identified which modulate proliferation or neuronal output from specific precursor groups, and one new gene target has been engineered into a new fate mapping tool useful for further subdivision of cell lineages. Altogether, experiments in this project will identfy precursor cell types and subtypes with unprecedented clarity and isolate key differentially expressed genes. These cell type- specific target genes will then be tested in a series of in vivo experiments for their role(s) in neurogenesis and neuronal positioning.

 描述（由申请人提供）：发育神经生物学的两个主要目标是鉴定形成中枢神经系统的生殖细胞，并表征这些细胞产生适当数量和类型的神经元的细胞和分子机制。这一建议代表了我们正在进行的努力，以精确地定义存在于哺乳动物新皮层壁中的每种神经前体类型的分子和形态学身份。在这个项目中，波士顿大学的Haydar实验室与耶鲁大学的Sestan实验室合作，对前体群体进行遗传命运作图，然后在批量和单细胞水平上进行下一代RNA测序。几个差异表达的基因已经被确定，调节增殖或神经元输出从特定的前体组，和一个新的基因靶已被工程改造成一个新的命运映射工具，用于进一步细分的细胞谱系。总之，本项目的实验将以前所未有的清晰度识别前体细胞类型和亚型，并分离关键的差异表达基因。然后将在一系列体内实验中测试这些细胞类型特异性靶基因在神经发生和神经元定位中的作用。