NEUROBIOLOGY OF SULFATED GLUCURONYL GLYCOCONJUGATES

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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.