Letters to Nature

Nature 423, 443-448 (22 May 2003) | doi:10.1038/nature01635; Received 28 January 2003; Accepted 21 March 2003

Chondroitin proteoglycans are involved in cell division of Caenorhabditis elegans

Souhei Mizuguchi1,2, Toru Uyama3, Hiroshi Kitagawa3, Kazuko H. Nomura1,2,4, Katsufumi Dejima1,2, Keiko Gengyo-Ando5, Shohei Mitani4,5, Kazuyuki Sugahara3 & Kazuya Nomura1,2,3

  1. Department of Biology, Faculty of Sciences 33, Kyushu University, Fukuoka 812-8581, Japan
  2. SORST, Kawaguchi Center Bldg, 4-1-8 Hon-cho, Kawaguchi, Saitama 332-0012, Japan
  3. PRESTO (Japan Science and Technology Corporation) Kawaguchi Center Bldg, 4-1-8 Hon-cho, Kawaguchi, Saitama 332-0012, Japan
  4. Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan
  5. Department of Physiology, Tokyo Women's Medical University School of Medicine, Tokyo 162-8666, Japan

Correspondence to: Kazuyuki Sugahara3Kazuya Nomura1,2,3 Correspondence and requests for materials should be addressed to K.N. (Email: knomuscb@mbox.nc.kyushu-u.ac.jp) or K.S. (Email: k-sugar@kobepharma-u.ac.jp). Sequences of the longer ChSy and the shorter ChSy have been deposited in the DNA Data Bank of Japan under accession numbers AB088397 and AB088398, respectively.

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.