REGULATION OF MYELINATION

雪旺细胞调控血管生成因子表达的调控机制 髓鞘特异性糖偶联物将在存在和 在不同水平的雪旺细胞中缺乏髓鞘组装和 大鼠坐骨神经模型的分化：新生、 组织培养后的新生儿，正常成人，粉碎成人，横切 成年人。本研究计划的具体目标包括：1)控制PO 基因表达：PO mRNA生物合成与稳态水平的关系 利用PO的体外无细胞翻译和体内生物合成 确定控件是否处于转录、翻译和/或 这些模型中的翻译后水平；2)分子分类和 PO的细胞内靶向性：定量测定细胞内PO的生物合成 在溶酶促进剂存在的情况下切断神经，以确定 横断区雪旺细胞向溶酶体靶向PO的途径 神经，并确定PO上负责分类的信号 溶酶体分娩；3)诱导新生儿雪旺氏细胞PO翻译 共培养后的细胞：评估与 培养的新生儿雪旺细胞中PO基因的转录调控； 雪旺细胞糖脂生物合成的改变：进一步 研究与生物合成转移相关的控制机制 从半乳糖脑苷脂和单半乳糖二酰甘油 髓鞘的组装和维持对葡萄糖脑苷脂和 低聚己糖神经酰胺缺乏髓鞘组装。这是意料之中的 这种方法将提高我们对分子的理解 与髓鞘形成过程的启动有关的机械性运动。在……里面 此外，有关与以下各项相关的监管事件的信息 髓鞘形成应该被证明有助于理解人类疾病， 例如炎症性脱髓鞘周围神经病。

The regulatory mechanisms by which Schwann cells control the expression oif myelin specific glycoconjugates will be evaluated in the presence and absence of myelin assembly and during various levels of Schwann cell differentiation in the following rat sciatic nerve models: neonatal, neonatal after tissue culture, normal adult, crushed adult, and transected adult. The specific aims of this research plan include 1) control of PO gene expression: to correlate PO mRNA biosynthesis and steady state levels with the in vitro cell-free translation and in vivo biosynthesis of PO to determine if the control is at the transcription, translation, and/or post-translation levels in these models; 2) molecular sorting and intracellular targeting of PO: to quantitate PO biosynthesis in the transected nerve in the presence of lysosomotropic agents, to determine the route of PO targeting to the lysosome by Schwann cells in the transected nerve, and to ascertain the sorting signal on PO responsible for the lysosomal delivery; 3) induction of PO translation in neonatal Schwann cells after co-culture: to evaluate the mechanisms associated with the translational control of PO mRNA in cultured neonatal Schwann cells; and 4) alterations in glycolipid biosynthesis by Schwann cells: to further examine the mechanisms of control associated with the biosynthetic shift from the galactocerebrosides and monogalactosyl diacylglycerol during myelin assembly and maintenance to the glucocerebrosides and oligohexosylceramides in the absence of myelin assembly. It is anticipated that this approach will improve our understanding of the molecular michanisms associated with the initiation of the myelinating process. In addition, information concerning the regulatory events associated with myelination should prove useful for understanding human disease involving, for example, the inflammatory demyelinating peripheral neuropathies.