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Caenorhabditis elegans early embryogenesis and vulval morphogenesis require chondroitin biosynthesis

Nature volume 423, pages 439–443 (2003)Cite this article

Abstract

Defects in glycosaminoglycan biosynthesis disrupt animal development and can cause human disease1,2,3,4. 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 development5,6. Seven of the eight sqv genes have been shown to control the biosynthesis of the glycosaminoglycans chondroitin and heparan sulphate6,7,8,9,10,11. 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.

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Figure 1: Sequence alignment of SQV-5 and homologues.
Figure 2: Glycosyltransferase activities were assayed using cell-free extracts prepared from wild type (+/+) and sqv-5(n3611) heterozygotes (-/+) and homozygotes (-/-).
Figure 3: Wild-type worms were stained with antibodies specific for SQV-5 and/or SQV-1 (ref.
Figure 4: Model of the function of SQV proteins in the biosynthesis of heparan and chondroitin backbones.

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Acknowledgements

We thank B. Castor for help with DNA sequencing; Y. Kohara for the cDNA clones yk20dy and yk21g9; A. Coulson for cosmids; J. Brown for the GlcAβ1,3Gal-O-NM acceptor; B. Zak for N-acetylheparosan acceptor; the Glycotechnology Core at UCSD (supported by an NIH grant) for the preparation of UDP-[1-3H]GlcA; and B. Galvin and I. Perez de la Cruz for reading the manuscript. This work was supported by NIH grants (to H.R.H. and J.D.E.). S.K.O. was supported by an NIH training grant. H.R.H. is an Investigator of the Howard Hughes Medical Institute.

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  1. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Room 68-425, 77 Massachusetts Avenue, Cambridge, Massachusetts, 02139, USA

    Ho-Yon Hwang & H. Robert Horvitz

  2. Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California, San Diego, 9500 Gilman Drive, CMM-East 1055, La Jolla, California, 92093, USA

    Sara K. Olson & Jeffrey D. Esko

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Correspondence to H. Robert Horvitz.

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Hwang, HY., Olson, S., Esko, J. et al. Caenorhabditis elegans early embryogenesis and vulval morphogenesis require chondroitin biosynthesis. Nature 423, 439–443 (2003). https://doi.org/10.1038/nature01634

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