Role of O-Glycosylation in Development Research

Glycosyltransferases in  C. elegans Development. The development of adult tissues and organs requires the integrated interactions of multiple tissues, cell-types and processes. We hypothesize that oligosaccharides on the cell surface are crucial for orchestrating development processes because glycoconjugates are expressed in regulated temporal and spatial patterns and because they are capable of modulate cellular interactions. We are utilizing the ppGaNTase gene family as molecular tools to understand how O-glycosylation is regulated during development in a well-defined animal model, Caenorhabditis elegans. The nematode C. elegans expresses a total of 13 ppGaNTase cDNAs through alternative message processing from 9 genes (gly-3 through gly-11) (see figure).

An expression pattern database for glycosyltransferase is currently being created through transgenic studies, and the roles of glycosyltransferase in development are being explored using reverse genetics. This approach, coupled with a detailed biochemical analysis of the ppGaNTase enzymes, will provide insights to fundamental developmental processed that lead to the formation of organs and oro-pharyngeal-head structures and tissues

figure legend.
Predicted protein domains of the C. elegans family of ppGaNTase sequence homologs. The N-terminus (left-end) of the polypeptides begins with the cytoplasmic domain followed by the transmembrane segment and then the region of the protein that exhibits catalytic activity. The gly-7::lacZ transgene indicates that ppGaNTase GLY-7 is exclusively expressed in the nematode pharynx. (middle panel) A DIC image of a nematode obtained from a mutant screen reveals a defect in head development (affected gene is unknown) (bottom panel).