CONTROL OF GRANULE CELL SPECIFICATION IN THE CEREBELLUM

小脑颗粒细胞规格的控制

基本信息

批准号：
6565241
负责人：
Mary Elizabeth Hatten
金额：
$ 25.59万
依托单位：
ROCKEFELLER UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-12-01 至 2002-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6565241
关键词：
Xenopus brain mapping cell cycle cell differentiation cell population study cerebellar cortex chick embryo developmental neurobiology early embryonic stage embryo /fetus tissue /cell culture gene expression granule cell in situ hybridization laboratory mouse neural plate /tube neurogenesis neurogenetics neuroregulation species difference transcription factor transforming growth factors vertebrate embryology video microscopy western blottings

Xenopus brain mapping cell cycle cell differentiation cell population study cerebellar cortex chick embryo developmental neurobiology early embryonic stage embryo /fetus tissue /cell culture gene expression granule cell in situ hybridization laboratory mouse neural plate /tube neurogenesis neurogenetics neuroregulation species difference transcription factor transforming growth factors vertebrate embryology video microscopy western blottings

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项目摘要

The overall goal of this project is to examine the control of granule neuron specification and differentiation in embryonic stages of vertebrate cerebellar development. In the first group of experiments, expression of the zinc finger transcription factor RU49 will be used to map the earliest granule precursors in the midbrain/hindbrain region of mouse embryos ib embryonic days 9.5 through 13.5. The second set of experiments will localize expression of the TGFbeta family of growth factors (BMP6, BMP7 or GDF7) in the midbrain/hindbrain region of the neural tube, and test the role of these factors in induction of RU49. In a third set of experiments, the role of the basic helix loop helix transcription factor Math-1 (atonal) in EGL cell specification and differentiation will be studied Expression of Math-1 will be defined in situ hybridization of mRNAs in vivo between E8.0 and p15, as well as in cultures of purified progenitor cells and the function of Math-1 will be investigated by over-expression of the gene and by expression of a dominant negative form of the gene. In a fourth group of experiments, video microscopy will be used to define the mitotic activity and mode of movement of progenitor cells within the rhombic lip cells during the initial steps of the formation of the external germinal layer (EGL). The relationship between cell division and movement of cells onto the surface of the cerebellar anlage will be examined by tracing dye-labeled cells in explants of embronic midbrain/hindbrain tissue. The behavior of cells in the rhombic lip will be compared among three vertebrates: Mus musculis, Gallus domesticus and Xenopus laevis.

该项目的总体目标是检查颗粒的控制脊椎动物胚胎阶段的神经元规范和分化小脑开发。在第一组实验中，表达锌指转录因子RU49将用于绘制最早的绘制小鼠胚胎IB的中脑/后脑区域的颗粒前体胚胎第9.5至13.5天。第二组实验将 TGFBETA生长因子家族的本地化表达（BMP6，BMP7或 GDF7）在神经管的中脑/后脑区域中，并测试这些因素在RU49诱导中的作用。在第三组实验中，基本螺旋环螺旋转录因子Math-1的作用（Atonal）将研究EGL细胞规范和分化 Math-1的表达将定义在原位mRNA中的原位杂交 E8.0和P15之间以及纯化祖细胞培养物之间的体内细胞和Math-1的功能将通过过表达研究基因和基因的主要负面形式的表达。在第四组实验中，视频显微镜将用于定义有丝分裂活性和祖细胞运动方式在形成的初始步骤中，在菱形唇部细胞内外部生发层（EGL）。细胞分裂之间的关系细胞将细胞移至小脑表面，将是通过追踪染料标记的细胞中的染色器中的外植体检查中脑/后脑组织。菱形唇中细胞的行为将在三个脊椎动物中进行比较：Mus Musculis，Gallus fimderus和 Xenopus laevis。