Abstract
We have revealed that in Caenorhabditis elegans, non-sulfated chondroitin is required for normal cell division and cytokinesis at an early developmental stage, whereas heparan sulfate is essential for embryonic morphogenesis in the later stages of development. To clarify the roles of chondroitin sulfate and heparan sulfate in early embryogenesis in mammals, we generated glucuronyltransferase-I (GlcAT-I) knock-out mice by gene targeting. GlcAT-I is an enzyme required for the synthesis of both chondroitin sulfate and heparan sulfate. Here we report that mice with a deletion of GlcAT-I showed remarkable reduction of the synthesis of chondroitin sulfate and heparan sulfate and embryonic lethality before the 8-cell stage because of failed cytokinesis. In addition, treatment of wild-type 2-cell embryos with chondroitinase ABC had marked effects on cell division, although many heparitinase-treated embryos normally developed to blastocysts. Taken together, these results suggest that chondroitin sulfate in mammals, as with non-sulfated chondroitin in C. elegans, is indispensable for embryonic cell division.
Highlights
Chondroitin sulfate (CS),3 dermatan sulfate (DS), heparan sulfate (HS), and heparin (Hep) are a class of glycosaminoglycans (GAGs) that distribute on the surfaces of virtually all cells and in the extracellular matrices
We have revealed that in Caenorhabditis elegans, non-sulfated chondroitin is required for normal cell division and cytokinesis at an early developmental stage, whereas heparan sulfate is essential for embryonic morphogenesis in the later stages of development
Treatment of wild-type 2-cell embryos with chondroitinase ABC had marked effects on cell division, many heparitinase-treated embryos normally developed to blastocysts. These results suggest that chondroitin sulfate in mammals, as with non-sulfated chondroitin in C. elegans, is indispensable for embryonic cell division
Summary
The mutant allele was detected as a 550-bp band using primers c and d and the wild-type allele was detected as a 100-bp band using primers a and b. Knock-out mice and attempted to analyze in vivo functions of CS/DS at an early developmental stage. We demonstrated that most homozygous null mice die by embryonic day 2.5 because of failure of cytokinesis. Almost all embryos treated with chondroitinase ABC died from 2-cell to 8-cell stages, whereas many heparitinase-treated embryos developed normally to blastocysts. These results suggest that CS is indispensable for early embryonic cell division in mammals
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
