AXONAL AND DENDRITIC DIFFERENTIATION IN GRANULE NEURONS

描述：本提案的目的是了解 其控制颗粒中轴突和树突分化和形态 神经元 为了确定细胞内在的线索，或存在于细胞中的线索， 细胞外环境，直接分化和成熟 颗粒细胞轴突和树突，将测试以下假设： 1)单极过程扩展的初始位置由 高尔基体的细胞质位置;单极延伸后， GA在细胞质内重新定向，以支持第二个细胞的生长。 轴突突 为了验证这一假设，延时共聚焦显微镜 将用于确定GA在初始阶段的动态行为， 颗粒细胞轴突生长的阶段。 2)初始双极并联后 纤维（PF）轴突生长完成，可扩散或接触介导 来自发育中的浦肯野细胞（PC）和/或颗粒细胞的信号 分子层（ML）引起轴突表达下调 细胞粘附分子TAG-1在深部颗粒细胞上的表达 颗粒层（EGL）/ML边界。 为了验证这一假设，将确定 无论是颗粒细胞/PC接触，还是模拟 颗粒细胞和Pcs之间突触活动，为 TAG-1在初始颗粒细胞轴突上的表达。 3)未成熟的暴露 颗粒细胞去极化条件抑制轴突生成，并促进 树突状分化 为了验证这一假设， 将从电镀时起暴露在去极化条件下。 四、 完整的颗粒细胞树突状分化，其特征在于： 特征爪状树突的形成，只有在 与苔藓纤维传入的直接细胞-细胞接触。 为了验证这一 假设，颗粒细胞将与脑桥外植体共培养， 提供苔藓纤维传入输入的来源，以确定是否直接 细胞与苔藓纤维的接触“驱动”了进一步的树突 分化 了解控制正常的机制 颗粒神经元的分化是理解病因的关键 各种小脑共济失调和出生缺陷，如胎儿酒精， 综合征

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.