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OHSU researchers discover molecular signaling system controlling aspects of embryonic development

al destiny, specifying the organ or tissue they will ultimately become. While scientists have long known that signals exchanged between cells control this process, little is known about the intricacies of these developmental systems.

This research showed that the Jeb protein controls the choice of certain embryonic cells between two fates. The cells that receive the Jeb signal become "founder cells" that function as pioneers to organize the development of smooth muscle. Cells that do not get the Jeb signal become "fusion cells" that attach to and fuse with founder cells to augment muscle mass.

This work established the essential signaling role of the Jeb protein. However, the identity of the molecular "Jeb-sensor" remained unknown. Finding this receptor was crucial to provide the complete molecular foundation needed for developing new drugs.

"Receptor and signal pairs are ideal targets for medicines because this is where human biology gets very specific. Identifying the players allows us to design drugs targeted at a precise molecular interaction. These types of drugs tend to have the maximum therapeutic impact with the fewest side effects," said Weiss.

Previous independent studies had identified a cell-surface receptor protein called anaplastic lymphoma kinase (Alk) in the late 1990s. All that was known about human Alk was that it could cause lymphoma if abnormally regulated; its normal function had not been determined.

After initial publication of Weiss's research on Jeb, scientists at New York's Mt. Sinai School of Medicine observed that the published expressions of Alk and Jeb appeared compatible and hypothesized that Jeb could be the protein that activates the Alk receptor. Subsequent collaborative studies between OHSU and Mt. Sinai researchers in fruit flies confirmed this hypothesis.

In addition to identifying a central signaling pathway for smooth muscle development, these collaborative results have expand
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Contact: Christine Pashley
pashleyc@ohsu.edu
503-494-8231
Oregon Health & Science University
28-Oct-2003


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