NEUROBIOLOGY OF SULFATED GLUCURONYL GLYCOCONJUGATES

描述：(改编自申请者摘要)这项计划的主要目标 该项目是为了了解细胞表面磺基葡萄糖醛酸基的作用 糖脂(SGGL)和糖蛋白(SGGP) 在神经系统发育过程中受到特别调节。 与单抗HNK-1反应的磺基葡萄糖醛酸基碳水化合物， 专门表达在一组重要的分子上，这些分子 参与细胞间的相互作用和黏附。已经有人提议 磺基葡萄糖醛酸基碳水化合物参与了细胞 分化和细胞间的相互作用。 本文着重阐述了这一概念的表达、调控和功能。 碳水化合物，尤其是SGGL上的，在胚胎发育和 大脑皮层和小脑的新生儿发育。确实有 三个具体目标：1)确定SGGL是否在 未成熟外颗粒细胞在新生儿小脑内的迁移 检验SGGLS表达下调与 对这些细胞的成熟，2)确定是否下调 SGGL的合成导致可塑性的丧失和 中枢神经系统的再生，以及3)检验HNK-1的假设 新生内颗粒中原始星形胶质细胞上的碳水化合物 小脑细胞层，是迁移颗粒的“停止信号” 细胞。这些研究将在已知的小鼠模型上进行 神经细胞异常迁移与发育缺陷 系统以及在正常小鼠身上也是如此。结果应该会产生 关于HNK-1碳水化合物在细胞中作用的基本信息- 发育中的大脑中的细胞相互作用和迁移 定义这些过程中涉及的分子机制。它应该是 也有助于了解大脑发育异常以及 最终有能力进行临床干预以纠正神经学 涉及神经细胞迁移的疾病。

DESCRIPTION: (adapted from Applicant's Abstract) The major goal of this project is to understand the role of cell surface sulfoglucuronyl glycolipids (SGGLs) and glycoproteins (SGGPs) which are stage specifically regulated during development of the nervous system. Sulfoglucuronyl carbohydrate, reactive with monoclonal antibody HNK-1, is specifically expressed on an important group of molecules that are involved in cell-cell interaction and adhesion. It has been proposed that the sulfoglucuronyl carbohydrate is involved in cell differentiation and cell-cell interactions. This proposal focuses on the expression, regulation and function of this carbohydrate, especially on SGGLs, during embryonic development and neonatal development of the cerebral cortex and cerebellum. There are three specific aims: 1) to determine whether SGGLs are expressed in migrating immature external granule cells in neonatal cerebellum and to test the hypothesis that down-regulation of SGGLs expression is related to maturation of these cells, 2) to determine whether down-regulation of the synthesis of SGGLs contributes to the loss of plasticity and regeneration in the CNS, and 3) to test the hypothesis that HNK-1 carbohydrate, on primitive astrocytes in the nascent internal granule cell layer of cerebellum, is a "stop-signal" for migrating granule cells. These studies will be carried out on murine models known to have abnormal cellular migration and developmental defects in the nervous system as well as on normal mice. The results should generate fundamental information about the role of HNK-1 carbohydrate in cell- cell interactions and migration in the developing brain and further define the molecular mechanisms involved in these processes. It should also contribute to understanding abnormal brain development as well as to the eventual ability to intervene clinically to correct neurological disorders involving neuronal cell migration.