Cell-surface molecules have possible role in development and birth defects

St. Louis, Jan. 18, 2001 During pregnancy, an egg composed of one cell develops into a baby with more than 200 types of cells and all the tissues and organs needed for life. Understanding how this happens is one of the most interesting puzzles of human development, but investigators at Washington University School of Medicine in St. Louis are making progress.

A team led by Scott Saunders, M.D., Ph.D., assistant professor of molecular biology and pharmacology and of pediatrics, is unraveling the role played by a little-understood family of molecules called heparan sulfate proteoglycans (HSPGs) in determining a cells ultimate fate.

Our findings help explain how normal development is regulated and may provide insights into the cause of certain birth defects and cancers, says Saunders, who also is a member of the Siteman Cancer Center. The study appears in the Jan. 18 issue of The Journal of Biological Chemistry.

Saunders treats children with Simpson-Golabi-Behmel syndrome, a rare disease associated with mutations in HSPGs that often results in an enlarged head and body, in bone abnormalities including extra or fused fingers and toes, and in certain childhood cancers. His laboratory research seeks to understand how defects in HSPGs cause the syndrome.

His study revealed that HSPGs help regulate the presence of another group of proteins called morphogens. Morphogens influence cell development and differentiation and play an essential role in the formation of limbs and organs. During development, they diffuse through the spaces between cells to other areas of the embryo, creating a gradient of concentration.

Cells sense how much morphogen is outside their membranes, and this directs a cells fate, says Saunders. It is believed that the diffusion of other proteins known as antagonists, which bind to these morphogens and block their f unction, also help to determine the amount of signal that a given cell receives.

But dif

Contact: Darrell E. Ward
Washington University School of Medicine

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