sqv-3, -7, and -8, a set of genes affecting morphogenesis in Caenorhabditis elegans, encode enzymes required for glycosaminoglycan biosynthesis

^†Department of Molecular and Cell Biology, Boston University, Boston, MA 02118; ^‡Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California at San Diego, La Jolla, CA 92093; and ^§Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721

Contributed by Phillips W. Robbins

Abstract

sqv (squashed vulva) genes comprise a set of eight independent loci in Caenorhabditis elegans required zygotically for the invagination of vulval epithelial cells and maternally for normal oocyte formation and embryogenesis. Sequencing of sqv-3, sqv-7, and sqv-8 suggested a role for the encoded proteins in glycolipid or glycoprotein biosynthesis. Using a combination of in vitro analysis of SQV enzymatic activities, sqv ⁺ -mediated rescue of vertebrate cell lines, and biochemical characterization of sqv mutants, we show that sqv-3, -7, and -8 all affect the biosynthesis of glycosaminoglycans and therefore compromise the function of one specific class of glycoconjugates, proteoglycans. These findings establish the importance of proteoglycans and their associated glycosaminoglycans in epithelial morphogenesis and patterning during C. elegans development.

Footnotes

↵ * D.A.B., G.W., H.T., and A.K.-T. contributed equally to this work.
↵ ¶ To whom reprint requests should be addressed. E-mail: selleck{at}u.arizona.edu.
Abbreviations:

GlcA,

glucuronic acid;

GlcNAc,

N-acetylglucosamine;

GalNAc,

N-acetylgalactosamine;

Gal,

galactose;

FGF,

fibroblast growth factor;

CHO,

Chinese hamster ovary;

NM,

naphthalenemethanol;

UA,

uronic acid