Heterogeneity of Forebrain Neural Precursors

 描述(申请人提供)：发育神经生物学的两个主要目标是鉴定构成中枢神经系统的生发细胞，并描述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，以精确定义存在于哺乳动物新皮质壁上的每一种神经前体类型的分子和形态特征。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图谱绘制，然后在整体和单细胞水平上进行下一代RNA测序。一些差异表达的基因已经被鉴定出来，它们调控着特定前体群体的增殖或神经元输出，一个新的基因靶点已经被设计成一个新的命运图谱工具，有助于进一步细分细胞谱系。总之，该项目中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。这些特定细胞类型的靶基因随后将在一系列体内实验中进行测试，以确定它们在神经发生和神经元定位中的作用(S)。

 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.