Saunders and his colleagues studied the interaction of a morphogen known as bone morphogenic protein (BMP) and one of its antagonists, called noggin, in adult hamster cells.
The team discovered that noggin binds with certain HSPGs as well as with BMP. The HSPGs were found to anchor noggin to the surface of cells expressing the HSPGs. This implies that HSPGs can indirectly control the amount of BMP reaching a cell by regulating the location of this antagonist.
Saunders explaines that if the same interactions occur in growing embryos, it suggests a mechanism for the formation of complex morphogen gradients that regulate the development of bones, limbs and other organs. That hypothetical mechanism begins when an antagonist like noggin is released by a group of cells in one area of the embryo and diffuses through the spaces between cells to other areas of the embryo.
High levels of noggin would exist near the site of release, with decreasing levels further away. It also means that lower levels of BMP would be available to signal cells close to the site of noggin release and higher levels would be available at a distance.
The presence of noggin-binding HSPGs on the surface of some cells along the path of noggin diffusion might normally limit this diffusion and therefore noggins range of action.
On the other hand, a defect in the HSPGs might result in altered diffusion of noggin resulting in some cells seeing abnormally low levels of BMP, which would alter the fate of the cells.
Saunders findings may have other applications as well. Children born with Simpson-Golabi-Behmel syndrome, for example, are at higher risk for certain cancers. Also, the same HSPG gene that is mutated in these children often is disrupted in cancer cells from ovarian and br
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Contact: Darrell E. Ward
wardd@msnotes.wustl.edu
314-286-0122
Washington University School of Medicine
18-Jan-2002