SEQUENTIAL EVENTS IN NEURITE OUTGROWTH AND STABILIZATION

在突触发生之后，广泛交叉连接的基础设施 轴突在整个生命周期中基本保持不变 因此，轴突细胞骨架的稳定可能是 这是建立成熟神经元形态的关键事件，并且，在 反过来，神经系统的有序发育和维持 它的功能。然而，目前还不清楚神经元是如何启动的 轴突生长，并随后影响其有序过渡 轴突细胞骨架从推测灵活的结构中迅速- 生长中的轴突向成熟的稳定网架特征 轴突。 在胚胎大脑发育期间，有一段时间窗 迁移后的中性粒细胞含有足够的蛋白质池。 神经发生所必需的成分。最初的事件， 与蛋白质合成无关地发生，包括转位 先前建立的膜相关池、膜骨架池、 和细胞骨架蛋白注入到新设计的轴突中。这些 表观事件之后是成熟的轴突的建立 细胞骨架--这一过程依赖于合成和 额外蛋白质种类的翻译后修饰。我们的 结果进一步表明，某些蛋白质成分是 具体参与了神经突起的阐述，并且是 随后被其他(或在某些情况下，其异构体)取代 物业已经因为迟来的出现而被彻底改变 翻译后修饰语)，它调解了 轴突细胞骨架格子。 拟议的实验旨在阐明(1)哪些是 在未分化的细胞中存在足够的相关蛋白质 在缺乏放射源的情况下支持神经营养发生的数量 合成，以及它们移位到轴突的顺序；(2) 哪些物种或亚型只出现在与分化相关的 基因表达的变化；以及，最后，(3)哪些成分 赋予细胞骨架晶格稳定性，以及它们处于什么阶段 出现。

Following synaptogenesis, the extensively cross-linked infrastructure of an axon may remain basically unaltered throughout the lifetime of the neuron; accordingly, the stabilization of the axonal cytoskeleton may be a key event in the establishment of mature neuronal morphology, and, in turn, the orderly development of the nervous system and maintenance of its functionality. However, it remains unclear how a neuron initiates neurite outgrowth, and subsequently effects the orderly transition of its axonal cytoskeleton from the presumably flexible structure of a rapidly- growing neurite to the stabilized latticework characteristic of mature axons. During embryonic brain development, there is a window of time in which the postmigratory neuoblast contains sufficient pools of protein constituents necessary for neuritogenesis. The initial events, which occur independently of protein synthesis encompass the translocation of previously established pools of membrane-associated, membrane-skeletal, and cytoskeletal proteins into the newly-elaborated neurite. These epignetic events are followed by the establishment of a mature axonal cytoskeleton -- a process which is dependent upon synthesis and posttranslational modification of additional protein species. Our results further indicate that certain protein constituents are specifically involved in the elaboration of neurites, and are subsequently replaced by others (or, in some cases, isoforms whose properties have been drastically altered by late-appearing posttranslational modifications) which mediate stabilization of the axonal cytoskeletal lattice. The proposed experiments are designed to elucidate (1) which of the relevent proteins are present in undifferentiated cells in sufficient quantities to support neuritogenesis in the absence of aditional synthesis, and in what order they are translocated into the axon; (2) which species or isoforms appear only following differentiation-related alterations in genetic expressiom; and, finally, (3) which constituents confer stability to the cytoskeletal lattice and at what stage they appear.