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Sugars play an unexpected role in animal development

Chains of sugars called chondroitin play an important role in animal development, MIT researchers reported in the May 22 issue of Nature.

Chondroitin sulphate (CS) is found in cartilage and has been known to biologists for much of the 20th century, but has not been considered an important player in development. CS is secreted outside the cell and is a member of a group of sugar-polymers called glycosaminoglycans.

In humans, large amounts of CS are present in the extracellular matrix of cartilage, where CS plays a structural role. A modified form of CS called dermatan is a major component of skin.

In their studies of the nematode Caenorhabditis elegans, the researchers found that biosynthesis of chondroitin is required for normal embryo and organ development -- in this case the organ being the nematode's vulva, through which sperm and eggs pass.

"Our paper suggests that chondroitin influences cell shape changes during the first cell division in embryos and later during organ development," said H. Robert Horvitz, the Koch Professor of Biology at MIT, an investigator for the Howard Hughes Medical Institute and MIT's McGovern Institute for Brain Research, and a 2002 recipient of the Nobel Prize for physiology or medicine.

"Chondroitin seems to modify cell shape from outside the cells, most likely through the molecule's ability to interact with water, leading to swelling and a pressure against the cells," said Ho-Yon Hwang, a postdoctoral associate in MIT's Department of Biology.

Mutations in the biosynthesis of CS, dermatan and other glycocaminoglycans have been implicated in human diseases, such as an aging variant of the connective-tissue disorder Ehlers-Danlos syndrome, which is characterized by prematurely aged appearance, too-flexible joints and loose skin.

A better understanding of the biological roles of genes required for the biosynthesis of glycosaminoglycans could lead to diagnosis and better understanding of this aging disease and other similar diseases.

In addition to Hwang and Horvitz, the paper's authors include Sara Olson and Jeffrey Esko of the Glycobiology Research and Training Center at the University of California at San Diego.

This work was supported by the National Institutes of Health and by the Howard Hughes Medical Institute.

A version of this article appeared in MIT Tech Talk on June 4, 2003.

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