NEUROGENESIS IN THE MAMMALIAN CEREBELLUM

该项目的总体目标是提供有关 控制颗粒细胞命运规范的机制 小脑皮层。在拟议的研究中，我们将在 细胞和分子水平，控制分化的信号 起源于外生发层的前体细胞 小鼠小脑皮质，使用我们开发的体外模型系统 实验室。将解决两个问题。首先，我们将确定 生长因子，特别是那些高水平表达的生长因子 小脑发育中碱性成纤维细胞生长因子、神经营养因子和神经营养因子对颗粒细胞的调节作用 规格。第二，提供颗粒细胞的遗传分析 确定后，我们将从神经学角度分析EGL前体细胞 突变的小鼠织布者，一种颗粒细胞表型缺陷的动物 分化，包括失败的轴突生长和神经胶质引导 迁移。

The overall goal of this project is to provide information on the mechanisms that control the specification of granule cell fate in the cerebellar cortex. In the proposed research, we will examine, at the cellular and molecular levels, the signals that control the differentiation of precursor cells derived from the external germinal layer (EGL) of the mouse cerebellar cortex, using an in vitro model system developed in our laboratory. Two issues will be addressed. First, we will determine whether growth factors, in particular those with high levels of expression in developing cerebellum (bFGF, NT3 and BDNF) regulate granule cell specification. Second, to provide a genetic analysis of granule cell determination, we will analyze EGL precursor cells from the neurological mutant mouse weaver, an animal with phenotypic defects in granule cell differentiation, including a failure of neurite outgrowth and glial-guided migration.