Caenorhabditis elegans early embryogenesis and vulval morphogenesis require chondroitin biosynthesis

Abstract

Defects in glycosaminoglycan biosynthesis disrupt animal development and can cause human disease. So far much of the focus on glycosaminoglycans has been on heparan sulphate. Mutations in eight squashed vulva (sqv) genes in Caenorhabditis elegans cause defects in cytokinesis during embryogenesis and in vulval morphogenesis during postembryonic development. Seven of the eight sqv genes have been shown to control the biosynthesis of the glycosaminoglycans chondroitin and heparan sulphate. Here we present the molecular identification and characterization of the eighth gene, sqv-5. This gene encodes a bifunctional glycosyltransferase that is probably localized to the Golgi apparatus and is responsible for the biosynthesis of chondroitin but not heparan sulphate. Our findings show that chondroitin is crucial for both cytokinesis and morphogenesis during C. elegans development.

Identification of a Novel Chondroitin Hydrolase in Caenorhabditis elegans

“…Fertilized eggs laid within 11-12 h of the RNA-mediated interference treatment could not complete cell division, particularly cytokinesis (7)(8)(9). These results demonstrated the critical roles of Chn in C. elegans.…”

Glycosylation Genes Expressed in Seam Cells Determine Complex Surface Properties and Bacterial Adhesion to the Cuticle of Caenorhabditis elegans

“…Given the sequence similarity among these genes, it seems likely that bus-4 also encodes a galactosyltransferase. However, another related gene in this group (sqv-5) encodes the nematode chondroitin synthase, acting to transfer both glucuronic acid and N-acetylgalactosamine to build up chondroitin sulfate chains (Hwang et al 2003); therefore, other possible enzymatic activities cannot be excluded for BUS-4.…”

“…Two sets of glycosylation genes that have better defined and more important roles in C. elegans biology are the sqv and bre genes. The eight sqv genes are all involved in chondroitin biosynthesis, and mutants in any of these genes exhibit a distinctive abnormal vulval morphogenesis phenotype (''squashed vulva'') together with maternal-effect lethality caused by defects in the fluid-filled space between the embryo and eggshell (Herman and Horvitz 1999;Hwang et al 2003). The five bre genes are required for synthesis of glycosphingolipids, and four of them encode glycosyltransferases that act consecutively to build up carbohydrate chains (Griffitts et al 2001(Griffitts et al , 2003.…”

Heparan 2-O-sulfotransferase,hst-2, is essential for normal cell migration inCaenorhabditis elegans

“…Seven of the eight sqv genes encode for enzymes involved in the biosynthesis of the common tetrasaccharide linkage of HS͞CS and in the synthesis and transport of nucleotide sugars (31)(32)(33)(34)(35). One of the genes, sqv-5, encodes the chondroitin polymerase, indicating a role for chondroitin in epithelial invagination (36,37). Although hst-2::GFP is expressed in the vulval precursor cells, we could not detect any defects in vulval morphogenesis in homozygous hst-2 (ok595) animals, suggesting that 2-O-sulfation is dispensable for vulval development.…”