Chondroitin and heparan sulphate, two types of glycosaminoglycan, are well-known sugar polymers in animals. Much more is known about heparan sulphate's involvement during development compared with chondroitin sulphate's, but, thanks to two reports in Nature, chondroitin is at last in the spotlight, and is now shown to be involved in Caenorhabditis elegans cytokinesis and morphogenesis.

The so-called squashed vulva (sqv) genes are important for embryonic development and postembryonic vulval morphogenesis, and seven of these are known to regulate the biosynthesis of chondroitin and heparan sulphate. Hwang et al. cloned the eighth sqv gene, sqv-5 , corresponding to the gene sequence T24D1.1 , which Mizuguchi et al. also cloned in a separate study.

The protein encoded by T24D1.1 is similar to both human chondroitin synthase and chondroitin N-acetylgalactosaminyltransferase, which are needed for the initiation and elongation of chondroitin chains, respectively. In C. elegans, though, SQV-5 — or chondroitin synthase (ChSy), as Mizuguchi et al. refer to it — carries out both functions; protein extracts prepared from worms homozygous for a sqv-5 null allele lacked both activities. And both groups reported a marked reduction in the levels of chondroitin in the absence of sqv-5/ChSy.

Both groups used conventional mutations or RNA interference (RNAi) — by feeding the worms dsRNA — to suppress sqv-5/ChSy expression. RNAi caused weaker defects compared with conventional mutations; ∼90% of embryos from RNAi-treated worms died whereas all embryos of conventional mutants died. Mizuguchi et al. also noticed that 60% of the survivors of RNAi treatment showed poor gonad formation and laid few, morphologically abnormal eggs. Hwang et al. reported that RNAi treatment reduced vulval extracellular spaces.

A closer look by Mizuguchi et al., using four-dimensional microscopy, showed severe cell-division defects. Embryonic cell division seemed to progress and then reverse (from 2 to 4, to 6 cells, to 4, to 6 cells, and so on), apparently as a result of incomplete cytokinesis. Eggs laid after longer RNAi treatment, which had even less chondroitin, underwent normal nuclear division, but failed to undergo cytokinesis altogether. So, if chondroitin is required for normal embryonic cell division and cytokinesis, it follows, then, that treating normal embryonic cells with chondroitinase should also induce similar phenotypes — which was indeed the case.

Consistent with a role for chondroitin in cytokinesis, early embryogenesis and morphogenesis, Mizuguchi et al. showed that chondroitin was present in the oocytes, the uterus, spermatheca and fertilized egg shells. The cell surfaces of early embryos expressed high levels, too. Using anti-SQV-5 antibodies, Hwang et al. observed punctate staining in the cytoplasm of the vulva, uterus and oocytes, similar to the staining pattern that had previously been observed for SQV-1 and SQV-7. So Hwang et al. propose that the chondroitin biosynthetic steps that are catalysed by these SQV proteins all occur in the same subcellular compartment — most probably, the Golgi apparatus.

Hwang et al. also propose that chondroitin's ability to interact with water, which would generate osmotic pressure, could well be responsible for its ability to expand extracellular space, on the basis that observed defects in the first embryonic cytokinesis and vulval morphogenesis occur concomitantly with a reduction in extracellular matrix size. Mizuguchi et al. also suggest that the role of chondroitin in cell division and cytokinesis could be a structural one, but raise the possibility that an unidentified chondroitin-dependent signalling event might be necessary for the completion of cytokinesis, and indicate that the possible relationship of chondroitin with components of the cell cycle and cytoskeleton requires investigation.