Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

OHSU researchers discover molecular signaling system controlling aspects of embryonic development

29.10.2003


Identification of ’Jelly Belly’ gene may lead to new drugs to combat heart disease, cancer and neurological disorders



Researchers at Oregon Health & Science University (OHSU) have identified a secreted signaling protein that regulates smooth muscle development in fruit flies. In the absence of a protein called "Jelly Belly (Jeb)," primitive smooth muscle cells fail to migrate or differentiate, according to study results published in the October 2 issue of Nature.
"Our research shows that Jelly Belly is required for the normal development of the smooth muscle that surrounds the gut in flies and we are investigating it in the arteries of mammals. It is also related to the development of heart muscle," said Joseph B. Weiss M.D., Ph.D., principal investigator and assistant professor (molecular medicine and cardiology), and Heart Research Center scientist in the OHSU School of Medicine.

Smooth muscles are involved in involuntary but essential functions, such as digestion and control of blood flow. Unlocking the genetic mechanisms controlling their embryonic development may allow scientists to understand better what triggers their abnormal growth. Human disorders that are linked to abnormal smooth muscle growth or function include high blood pressure, arteriosclerosis and congenital heart defects.



"Weiss has discovered a link in the chain of events that signals primitive cells in the fruit fly embryo to become muscle cells. The findings are key to our quest to identify embryonic genes that are linked to cardiac diseases," said Kent L. Thornburg, Ph.D., professor of medicine (cardiology) and director of the OHSU Heart Research Center. Molecules in fruit flies are functionally similar to molecules in humans typically allowing discoveries in fruit fly biology to be extrapolated to humans. Weiss’s findings also illuminate an aspect of how embryonic cells organize themselves into the complex body plans observed across the animal world, including humans. At the embryonic stage, identical primitive cells somehow "choose" a path that determines their biological 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 expanded the clinical applications of Weiss’s initial research. Given the role of Alk in cancer, Weiss speculates that other tumors caused by abnormal regulation of Jeb-like activators pf Alk, would respond to drugs that target the interaction between Jeb and Alk.

Further, other studies suggest that the Jeb-Alk signaling pathway may also be important in adults. So far, Weiss and colleagues have found the Jeb protein in adult neurons, hinting that this signaling mechanism may play an essential role in neurological function. Already, an independent study has found a Jeb-like molecule in an adult worm (C. elegans), which appears to play a role in learning and memory.

"The same molecules that regulate growth and development in embryos can be expected to play a role in adaptive functions in the adult," said Weiss.

Weiss is currently conducting research to determine the possible role of Jeb in the function of the normal nervous system and, by comparison, the role of the Jeb-Alk signaling mechanism in adult neurological disorders.


Weiss’s research is funded in part by the National Institutes of Health/National Heart, Lung and Blood Institute, Howard Hughes Medical Institute and the American Heart Association.

Christine Pashley | EurekAlert!
Further information:
http://www.ohsu.edu/

More articles from Life Sciences:

nachricht New application for acoustics helps estimate marine life populations
16.01.2018 | University of California - San Diego

nachricht Unexpected environmental source of methane discovered
16.01.2018 | University of Washington Health Sciences/UW Medicine

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

White graphene makes ceramics multifunctional

16.01.2018 | Materials Sciences

Breaking bad metals with neutrons

16.01.2018 | Materials Sciences

ISFH-CalTeC is “designated test centre” for the confirmation of solar cell world records

16.01.2018 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>