The role of O-GlcNAc Tranferase in zebrafish embryogenesis
Webster, Danielle M.
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The study of development addresses the question of how an organism is formed from a single cell. Cells communicate with each other to instruct the fate of their neighboring cells, induce cell death, cell migration and morphogenesis. Processes such as the induction of cell fate are controlled by secreted factors such as activin, BMP and Nodal signals. Signal transduction pathways transmit many of the secreted factors involved in the process of development. Typical signal transduction is mediated by modifying proteins with chemical groups, such as phosphorus that may change the activity of the cytoplasmic or nuclear proteins (Gilbert, 2000). This results in gene transcription or repression, which leads to changes in cell fate. Once cell fates are specified they organize themselves by migrating during a process known as morphogenesis. Cell migration and morphogenesis are controlled by other factors such as the cytoskeleton and cell-cell adhesion. To understand development it is important to understand how modifications alter protein activity. O-linked glycosylation is another common posttranslational modification found to be involved in development, however its role is not fully understood. Regulation of O-GlcNAc occurs in the nucleus and cytoplasm and modifies many proteins such as transcription factors, oncogenes and cytoskeletal proteins. O-GlcNAc Tranferase (OGT) is the enzyme that catalyzes the addition of O-GlcNAc. OGT controls various reactions potentially affecting the activity of many proteins involved in signal transduction. Much is known about the proteins it modifies by in vitro biochemical and genetic studies, but little is known about how the modification affects protein activity in vivo. We are examining the role of OGT during zebrafish embryogenesis. Unlike mammals, zebrafish have two ogt genes, which encode several isoforms of the protein. Embryos overexpressing or lacking the enzyme are slowed during epiboly and have dramatically altered morphology at 24hpf. Several factors involved in zebrafish epiboly such as E-cadherin and cytoskeletal proteins have been shown to be modified by OGT in cell culture. We have examined the role of OGT and its effects on these factors that affect epiboly. We found that OGT affects cell adhesion between blastomeres along the cytoskeleton.