SULFOGLUCURONYL (HNK-1) CARBOHYDRATE IN NEUROGENESIS

Eunice Kennedy Shriver Ctr Mtl Retardatn, Waltham MA

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Abstract

The long term goal of this study is to test the hypothesis that interaction of sulfoglucuronyl carbohydrate (SGC) and its binding protein (SBP) involve SBP-1 on neurons and its ligand SGC on processes on neurons and glia, thus providing a guidance (SGC) and its binding protein (SBP) involve SBP-1 on neurons and its ligand SGC on processes of neurons and glia, thus providing a guidance and signaling mechanism for cell migration and process outgrowth. A large number of experiments toward that goal are planned in the four aims. Specific Aim 1 is to study neurite outgrowth and neuronal migration in explant cultures of embryonic cerebral cortex and thick slice tissue culture systems. Various antibodies and glycolipids will be added to determine the effect on migration and neuritogenesis. Specific Aim 2 is to clone the GlcNAc-Tr that has been described as the key regulatory enzyme for synthesis of Lc0se3Cer, the SGGC precursor. The main approach will be expression cloning, with the alternative use of a suppression subtractive hybridization cDNA library they recently constructed. Specific Aim 3 is to investigate the role of GT gene expression in regulation of SGC synthesis on glycolipids and glycoproteins during development . One hypothesis is that GlcNAc-Tr will be involved in expression of sulfoglucuronyl glycolipid (SGGL) rather than glycoproteins bearing the SGC epitope, which would presumably utilize other GlcNAc transferases.