AXONAL AND DENDRITIC DIFFERENTIATION IN GRANULE NEURONS

描述：本提案的目的是了解这些机制 控制颗粒中轴突和树突的分化和形态 神经元。以确定单元格固有的提示或呈现在 细胞外环境，直接影响细胞的分化和成熟 颗粒细胞轴突和树突，将检验以下假说： 1)单极突起延伸的初始位置由 高尔基体的胞质定位；单极延伸后， GA在细胞质内重新定位以支持第二个 轴突。为了验证这一假设，时间推移共聚焦显微镜 将用于确定GA在初始 颗粒Clel轴突生长发育阶段。2)初始双极平行后 纤维(PF)轴突生长是完全的、可扩散的或接触介导的 发育中的浦肯野细胞(PC)和/或颗粒细胞发出的信号 分子层(ML)导致轴突表达下调 细胞黏附分子TAG-1，位于细胞外深层的颗粒细胞上 颗粒层(EGL)/ML边界。为了检验这一假设，它将确定 颗粒细胞/PC是否接触，或模拟发病的条件 颗粒细胞和PC之间的突触活动，为 TAG-1在初始颗粒细胞轴突上的表达。3)暴露不成熟 颗粒细胞去极化抑制轴突发生，促进轴突发生 树突分化。为了验证这一假设，未成熟的颗粒细胞 将从电镀时起暴露在去极化条件下。4) 完整的颗粒细胞树突状分化，其特征是 特征的爪状树枝晶的形成，只有在 细胞间直接接触苔藓纤维传入。为了测试这一点 假设，颗粒细胞将与脑桥外植体共培养 提供来源苔藓纤维的传入，以确定是否直接 细胞-细胞与苔藓纤维的接触推动进一步的树突 差异化。了解控制正常的机制 颗粒神经元的分化是理解其病因的关键 各种小脑性共济失调和出生缺陷，如胎儿酒精 综合症。

DESCRIPTION: The objective of this proposal is to understand the mechanisms that control axonal and dendritic differentiation and morphology in granule neurons. To determine how cues intrinsic to the cell, or present in the extracellular environment, direct the differentiation and maturation of granule cell axons and dendrites, the following hypotheses will be tested: 1) The initial site of unipolar process extension is determined by the cytoplasmic location of the Golgi apparatus; after unipolar extension, the GA re-orients within the cytoplasm to support the growth of the second axonal process. To test this hypothesis, time-lapse confocal microscopy will be used to determine the dynamic behavior of the GA during the initial stages of granule clel axon outgrowth in. 2) After initial bipolar parallel fiber (PF) axon outgrowth is completed, diffusible or contact-mediated signals from developing Purkinje cells (PC) and/or granule cells within the molecular layer (ML) cause a down-regulation in expression of the axonal cell adhesion molecule, TAG-1, on granule cells located at the deep external granule layer (EGL)/ML border. To test this hypothesis, it will determined whether granule cell/PC contact in , or conditions that mimic the onset of synaptic activity between granule cells and Pcs, provide an "off-signal" for TAG-1 expression on initial granule cell axons. 3) Exposure of immature granule cells to depolarizing conditions inhibits axonogenesis and promotes dendritic differentiation. To test this hypothesis, immature granule cells will be exposed to depolarizing condition from the time of plating in . 4) Complete granule cell dendritic differentiation, which is characterized by the formation of characteristic claw-like dendrites, proceeds only after direct cell-cell contact with mossy fiber afferents. To test this hypothesis, granule cells will be co-cultured with pontine explants to provide a source of mossy fiber afferent input, to determine whether direct cell-cell contact with mossy fibers 'drives' further dendritic differentiation. Understanding the mechanisms that control the normal differentiation of granule neurons is critical in understanding the etiology of the various cerebellar ataxias and birth defects such as fetal alcohol syndrome.