Requirement for a core 1 galactosyltransferase in the Drosophila nervous system:

Glycosylation is important in a lot of fundamental biological processes, including cell recognition, cell adhesion, and cell signaling. Mucin-type O-glycosylation involves the synthesis of glycoproteins, expressed in mucous secretions and as transmembrane proteins on the cell surfaces. However, the biological functions of mucin-type O-glycans remain incompletely understood. I have pursued genetic and biochemical studies to understand their importance during development in Drosophila. Mucin-type O-glycosylation is initiated by the attachment of N-acetylgalactosamine (GalNAc) to Ser or Thr residues, and then elongated by additional sugars. To examine the requirements for mucin-type glycosylation in Drosophila, I characterized the expression and phenotypes of core 1 galactosyltransferases (core 1 GalTs), which elongate O-GalNAc by adding galactose in a β1, 3 linkage. Among Drosophila core 1 GalTs, CG9520 (C1GalTA) is expressed in the amnioserosa and central nervous system. A null mutation in C1GalTA is lethal. The mutant animals show a morphogenetic defect in their central nervous system in which the ventral nerve cord is greatly elongated and the brain hemispheres are distorted. Lectin staining and blotting experiments confirmed that C1GalTA is required for the synthesis of Gal-ß1,3-GalNAc in vivo. Our observations establish a role for mucin-type O-glycosylation during neural development in Drosophila. Overexpression of C1GalTA causes a wing blistering phenotype, which occurs when adhesion between the two ventral and dorsal surfaces of the wing blade is lost, and is also commonly seen in integrin mutants. This result implicates mucin-type O-glycans in cell adhesion in the Drosophila wing blade. Altogether, these results suggest a role of mucin-type O-glycosylation in Drosophila development, including the morphogenesis of central nervous system and the formation of the wing blade.Ph.D.Includes bibliographical references (p. 90-94)by Yuh-Ru Li