PROTEINS TALENT FOR SPLITTING HELPS SHAPE LIMBS, NERVES

December 2, 1994
Media Contact:Michael Purdy
Phone: (410) 955-8725
E-mail: MPurdy@welchlink.welch.jhu.edu

A curious biochemical busybody known as a "hedgehog" protein, which may control the development of the central nervous system and limbs in humans and other organisms, may get its workload done by splitting itself in two, according to researchers at Johns Hopkins.

The new insight, reported in the December 2 issue of Science, advances scientists' understanding of the early stages of life, an area of research that could one day lead to treatments for developmental disorders in human embryos.

"Hedgehog proteins are always full of surprises," says Stephen Ekker, Ph.D., a postdoctoral fellow at The Johns Hopkins Medical Institutions and co-author of the report.

"They are unique, and they're answering a number of fundamental questions about the development of life forms ranging from fruit flies to humans" says Ekker.

The name of the protein, first identified at Hopkins in 1992, comes from an experiment with fruit fly larvae. These larvae normally grow thin rows of bristles on their body to help them move; when scientists remove the gene for the protein, the bristles grow all over the body instead of in rows, making it look like a hedgehog.

"Since then, we've identified hedgehog proteins in all the higher animals we've looked at, from the sea urchin through humans." says Ekker.

Previous research at other institutions and Hopkins has shown that surgically moving cells that produce hedgehog protein can dramatically reorganize the way limbs form in lab animals. Until now, though, scientists have had little direct evidence of how hedgehog protein works.

The protein seems to act like a stage director giving cues to performers in a play. Scientists think it bonds with individual cells and turns on and off genes in the cells that allow them to play their specialized roles in the development of an arm, a leg, or the spinal column.

"One puzzling feature of hedgehog activity, though, is that hedgehog protein seems to affect both the area where it was produced and cells some distance away," says John Lee, an M.D./Ph.D. student at Hopkins and lead author of the Science paper.

The new study, conducted on fruit flies, may explain how hedgehog protein accomplishes these different tasks. After hedgehog protein splits, the two fragments have different biochemical properties and are found in different areas of the developing fruit fly One fragment may direct the development of cells more distant from the site of its production, while another gives cues to cells near the area where it was produced.

Philip Beachy, Ph.D., an assistant professor of molecular biology and genetics, says researchers' next step will be to try to figure out the roles of the two fragments in a variety of lab organisms. "We're hoping that this will also help us learn some new things about the role hedgehog proteins play in human development," Beachy says.

Research into hedgehog proteins was funded by the Howard Hughes Institute for Molecule Genetics.


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