CONTROL OF GRANULE CELL SPECIFICATION IN THE CEREBELLUM

本项目的总体目标是研究颗粒控制 脊椎动物胚胎期神经元的特化和分化 小脑发育在第一组实验中， 锌指转录因子RU 49将被用来定位最早的 小鼠胚胎中脑/后脑区的颗粒前体 胚胎期9.5到13.5天。第二组实验将 局部表达TGF β家族的生长因子（BMP 6、BMP 7或BMP 8）， GDF 7）在中脑/后脑区域的神经管，并测试 这些因子在诱导RU 49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 （无调性）在EGL细胞特化和分化中的作用 Math-1的表达将被定义为： 在E8.0和p15之间的体内，以及在纯化的祖细胞的培养物中， 细胞和功能的数学-1将被调查的过度表达 基因的显性负性形式的表达。 在第四组实验中，视频显微镜将用于 定义祖细胞的有丝分裂活性和运动模式 在菱形唇细胞形成的最初步骤中， 外胚层（EGL）。细胞分裂与 细胞移动到小脑原基表面， 通过追踪胚胎外植体中的染料标记细胞来检查 中脑/后脑组织。菱形唇中细胞的行为 在三种脊椎动物之间进行比较：小家鼠、原鸡和 非洲爪蟾

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.