SEQUENTIAL EVENTS IN NEURITE OUTGROWTH AND STABILIZATION

突触发生后，广泛交联的基础设施， 轴突可以在整个生命周期中保持基本不变， 神经元;因此，轴突细胞骨架的稳定可能是 一个关键事件，在建立成熟的神经元形态，并在 反过来，神经系统的有序发展和维护， 它的功能性。 然而，目前还不清楚神经元如何启动 神经突生长，并随后影响其有序过渡 轴突细胞骨架从一个快速- 生长神经突到稳定的晶格特征的成熟 轴突 在胚胎大脑发育期间，有一个时间窗口， 迁移后的成神经细胞含有足够的蛋白质库 神经突发生所必需的成分。 最初的事件， 独立于蛋白质合成发生， 先前建立的膜相关，膜骨架， 和细胞骨架蛋白进入新的神经突。 这些 继受事件之后是成熟轴突的建立 细胞骨架-一个过程，这是依赖于合成和 其他蛋白质种类的翻译后修饰。 我们 结果进一步表明，某些蛋白质成分 特别是参与神经突的加工， 随后被其他的（或者，在某些情况下， 这些特性已经被后来出现的 翻译后修饰），其介导蛋白质的稳定。 轴突细胞骨架晶格。 所提出的实验旨在阐明（1） 相关蛋白质存在于未分化细胞中， 在缺乏维生素A的情况下支持轴突发生的量 合成，以及它们以何种顺序移位到轴突中;（2） 哪些物种或同种型仅在分化相关的 基因表达的改变;最后，（3）哪些成分 赋予细胞骨架晶格稳定性，以及在什么阶段 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.