EMBARGOED by NATURE for 1 pm EDT May 21, 2003

Researchers Show Importance of Chondroitin In Tissue and Organ Development

Researchers at Massachusetts Institute of Technology and the University of California, San Diego (UCSD) School of Medicine have reported in the May 22, 2003 issue of the journal Nature that chains of sugars called chondroitin play an important role in the development of tissues and organs in animals.

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 vulva, through which sperm and eggs pass.

Chondroitin sulfate (CS) is a member of a group of sugar-polymers called glycosaminoglycans found in cartilage. Although known to biologists for much of the 20th century, CS but has not been considered an important player in development. In humans, large amounts of CS are present in the extracellular matrix of cartilage, where it plays a structural role. A modified form of CS called dermatan is a major component of skin.

"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 paper's senior author and Koch Professor of Biology at MIT, an investigator for the Howard Hughes Medical Institute and McGovern Institute for Brain Research, and a 2002 recipient of the Nobel Prize for Physiology or Medicine.

Jeffrey D. Esko, Ph.D.

Jeffrey D. Esko, Ph.D., UCSD professor of Cellular and Molecular Medicine and one of the paper's authors, provided the biochemical analysis for the study. Esko is co-director of the UCSD Glycobiology Research and Training Center and President of the Society for Glycobiology.

"We found that chondroitin, which is related in structure to the chondroitin sulfate found in cartilage, is important in cell division and shape during development," Esko said. "One possibility is that chondroitin acts as a signaling molecule, but it's also possible that the effect is due to its biophysical properties."

"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, the paper's first author and a postdoctoral associate in MIT's Department of Biology.

Mutations in the biosynthesis of CS, dermatan and other glycosaminoglycans 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, Horvitz and Esko, an additional author was Sara Olson of the UCSD Biomedical Sciences graduate program.

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

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