NEUROBIOLOGY OF SULFATED GLUCURONYL GLYCOCONJUGATES

描述：（改编自申请人的摘要）本发明的主要目标是： 项目是了解细胞表面磺基葡萄糖醛酸的作用 糖脂（SGGL）和糖蛋白（SGGP）， 在神经系统的发育过程中受到特别的调节。 磺基葡萄糖醛酸碳水化合物，与单克隆抗体HNK-1反应， 在一组重要的分子上特异性表达， 参与细胞间相互作用和粘附。 已经提出 磺基葡萄糖醛酸基碳水化合物参与了 分化和细胞-细胞相互作用。 本建议着重于这一点的表达、调节和功能 碳水化合物，特别是SGGL，在胚胎发育过程中， 新生儿大脑皮层和小脑的发育。 有 三个具体目标：1）确定SGGL是否在 新生儿小脑中迁移的未成熟外部颗粒细胞， 检验SGGL表达下调与 2）确定是否下调这些细胞的成熟， SGGL的合成导致可塑性的丧失， 3）为了检验HNK-1在CNS中的再生的假设， 碳水化合物，在新生内部颗粒中的原始星形胶质细胞上 细胞层，是迁移颗粒的“停止信号 细胞 这些研究将在已知具有以下特征的鼠模型上进行： 异常细胞迁移和神经系统发育缺陷 系统以及正常小鼠。 结果应该产生 关于HNK-1碳水化合物在细胞中作用的基本信息- 在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。 应当 也有助于了解异常的大脑发育， 最终能够在临床上进行干预， 涉及神经元细胞迁移的疾病。

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.