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 Phage capsid against influenza: Perfectly fitting inhibitor prevents viral infection
31.03.2020 | Forschungsverbund Berlin

nachricht A 'cardiac patch with bioink' developed to repair heart
31.03.2020 | Pohang University of Science & Technology (POSTECH)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Physicist from Hannover Develops New Photon Source for Tap-proof Communication

An international team with the participation of Prof. Dr. Michael Kues from the Cluster of Excellence PhoenixD at Leibniz University Hannover has developed a new method for generating quantum-entangled photons in a spectral range of light that was previously inaccessible. The discovery can make the encryption of satellite-based communications much more secure in the future.

A 15-member research team from the UK, Germany and Japan has developed a new method for generating and detecting quantum-entangled photons at a wavelength of...

Im Focus: Junior scientists at the University of Rostock invent a funnel for light

Together with their colleagues from the University of Würzburg, physicists from the group of Professor Alexander Szameit at the University of Rostock have devised a “funnel” for photons. Their discovery was recently published in the renowned journal Science and holds great promise for novel ultra-sensitive detectors as well as innovative applications in telecommunications and information processing.

The quantum-optical properties of light and its interaction with matter has fascinated the Rostock professor Alexander Szameit since College.

Im Focus: Stem Cells and Nerves Interact in Tissue Regeneration and Cancer Progression

Researchers at the University of Zurich show that different stem cell populations are innervated in distinct ways. Innervation may therefore be crucial for proper tissue regeneration. They also demonstrate that cancer stem cells likewise establish contacts with nerves. Targeting tumour innervation could thus lead to new cancer therapies.

Stem cells can generate a variety of specific tissues and are increasingly used for clinical applications such as the replacement of bone or cartilage....

Im Focus: Artificial solid fog material creates pleasant laser light

An international research team led by Kiel University develops an extremely porous material made of "white graphene" for new laser light applications

With a porosity of 99.99 %, it consists practically only of air, making it one of the lightest materials in the world: Aerobornitride is the name of the...

Im Focus: Cross-technology communication in the Internet of Things significantly simplified

Researchers at Graz University of Technology have developed a framework by which wireless devices with different radio technologies will be able to communicate directly with each other.

Whether networked vehicles that warn of traffic jams in real time, household appliances that can be operated remotely, "wearables" that monitor physical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“4th Hybrid Materials and Structures 2020” takes place over the internet

26.03.2020 | Event News

Most significant international Learning Analytics conference will take place – fully online

23.03.2020 | Event News

MOC2020: Fraunhofer IOF organises international micro-optics conference in Jena

03.03.2020 | Event News

 
Latest News

Phage capsid against influenza: Perfectly fitting inhibitor prevents viral infection

31.03.2020 | Life Sciences

A 'cardiac patch with bioink' developed to repair heart

31.03.2020 | Life Sciences

Artificial intelligence can speed up the detection of stroke

31.03.2020 | Medical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>