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Chondroitin proteoglycans are involved in cell division of Caenorhabditis elegans

Nature volume 423, pages 443–448 (2003)Cite this article

Abstract

Glycosaminoglycans such as heparan sulphate and chondroitin sulphate are extracellular sugar chains involved in intercellular signalling. Disruptions of genes encoding enzymes that mediate glycosaminoglycan biosynthesis have severe consequences in Drosophila and mice1,2,3,4,5. Mutations in the Drosophila gene sugarless, which encodes a UDP-glucose dehydrogenase, impairs developmental signalling through the Wnt family member Wingless, and signalling by the fibroblast growth factor and Hedgehog pathways. Heparan sulphate is involved in these pathways6,7,8, but little is known about the involvement of chondroitin. Undersulphated and oversulphated chondroitin sulphate chains have been implicated in other biological processes, however, including adhesion of erythrocytes infected with malaria parasite to human placenta and regulation of neural development9,10. To investigate chondroitin functions, we cloned a chondroitin synthase homologue of Caenorhabditis elegans and depleted expression of its product by RNA-mediated interference and deletion mutagenesis. Here we report that blocking chondroitin synthesis results in cytokinesis defects in early embryogenesis. Reversion of cytokinesis is often observed in chondroitin-depleted embryos, and cell division eventually stops, resulting in early embryonic death. Our findings show that chondroitin is required for embryonic cytokinesis and cell division.

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Figure 1: Structure of chondroitin proteoglycan and the nematode ChSy gene.
Figure 2: Chondroitin in C. elegans and lethal phenotypes in ChSy-disrupted worms.
Figure 3: Depletion of chondroitin by RNAi treatment (feeding method) and the effects of chondroitin depletion on embryonic cytokinesis.
Figure 4: Reversion of cytokinesis in chondroitin-depleted embryos.

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Acknowledgements

We thank T. Stiernagle and the Caenorhabditis Genetics Center for all worms and E. coli strains, and Y. Kohara for the yk clones. K.N. was supported by PRESTO and SORST of the Japan Science and Technology Corporation (JST). S.M. and K.H.N. were supported partly by Sasakawa Scientific Research Grant (JSS). The work at Kobe Pharmaceutical University was supported in part by a Science Research Promotion Fund from the Japan Private School Promotion Foundation, and by Grants-in-Aid for Scientific Research C (to H.K.) and Scientific Research B (to K.S.) from the Ministry of Education, Science, Sports and Culture of Japan.

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Authors and Affiliations

  1. Department of Biology, Faculty of Sciences 33, Kyushu University, 812-8581, Fukuoka, Japan

    Souhei Mizuguchi, Kazuko H. Nomura, Katsufumi Dejima & Kazuya Nomura

  2. SORST, Kawaguchi Center Bldg, 4-1-8 Hon-cho, 332-0012, Kawaguchi, Saitama, Japan

    Souhei Mizuguchi, Kazuko H. Nomura, Katsufumi Dejima & Kazuya Nomura

  3. PRESTO (Japan Science and Technology Corporation) Kawaguchi Center Bldg, 4-1-8 Hon-cho, 332-0012, Kawaguchi, Saitama, Japan

    Kazuko H. Nomura & Shohei Mitani

  4. Department of Biochemistry, Kobe Pharmaceutical University, 658-8558, Higashinada-ku, Kobe, Japan

    Toru Uyama, Hiroshi Kitagawa, Kazuyuki Sugahara & Kazuya Nomura

  5. Department of Physiology, Tokyo Women's Medical University School of Medicine, 162-8666, Tokyo, Japan

    Keiko Gengyo-Ando & Shohei Mitani

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  1. Souhei Mizuguchi
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Correspondence to Kazuyuki Sugahara or Kazuya Nomura.

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Mizuguchi, S., Uyama, T., Kitagawa, H. et al. Chondroitin proteoglycans are involved in cell division of Caenorhabditis elegans. Nature 423, 443–448 (2003). https://doi.org/10.1038/nature01635

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