Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Deciphering DiGeorge syndrome

01.03.2005


Big advances in understanding microdeletions



A collaboration of European scientists has uncovered new insight into the most common chromosomal microdeletion syndrome in humans. The research group, headed by Dr. Lukas Sommer at the Swiss Federal Institute of Technology, has identified a heretofore unknown role for the TGF cell-to-cell signaling pathway in the pathogenesis of DiGeorge syndrome. By elucidating the genetic mechanism that drives DiGeorge syndrome, Dr. Sommer and colleagues are helping establish a foundation for the future design of therapies to better identify and treat this disease. "We now show that the growth factor TGF is a key signal for normal neural crest development: genetic inactivation of TGF signaling in mouse neural crest stem cells prevents neural crest cell differentiation and recapitulates all morphological features of DiGeorge syndrome," explains Dr. Sommer.

Their report will be published in the March 1 issue of the scientific research journal Genes & Development. DiGeorge syndrome is a congenital disease that annually affects about 1 in 4000 live births. DiGeorge patients display a broad range of symptoms, which may include cardiac defects, immunodeficiency, craniofacial malformations, learning disabilities, and psychiatric problems. DiGeorge patients are generally missing a small portion of chromosome 22. The genes which would normally reside on this area of the chromosome, but which are deleted in DiGeorge patients, direct embryonic development of the pharyngeal arches, an area of the fetus containing so-called "neural crest cells."


The neural crest is a group of cells that, during embryogenesis, segregates into smaller cell clusters and migrate to diverse locations within the embryo. Depending upon location, neural crest cells give rise to most of the peripheral nervous system, as well as various non-neural tissues, like craniofacial bone and cartilage, the thymus and parathyroid glands, and the cardiac outflow tract – in short, all of the tissues that are affected in DiGeorge syndrome.

While embryologists have long known what structures the neural crest contributes to, little is known about the molecular cues that guide this process. Dr. Sommer and colleagues set out to investigate the role of the TGF signaling pathway (already well-known for its role in regulating cell growth and proliferation in other cellular contexts) in the neural crest.

The researchers engineered a strain of mice to specifically lack a TGF receptor in their neural crest stem cells, thereby inactivating TGF signaling in the developing neural crest. Dr. Sommer and colleagues observed that these mice recapitulated all of the defects seen in DiGeorge patients: craniofacial, cardiac, thymic and parathyroid defects.

While neither TGF receptors nor ligands are housed in the deleted region of chromosome 22, Dr. Sommer and colleagues did identify that a protein called CrkL,which is encoded within that region and has been implicated in the development of DiGeorge syndrome, interacts with TGF signaling. The authors speculate that the deletion of CrkL in DiGeorge patients disrupts TGF signal activation and prevents normal development of the neural crest. Dr. Sommer and colleagues not only establish that TGF is a key signal in specifying non-neural cell fates from the neural crest, but they also link defects in TGF signaling to the development of DiGeorge syndrome.

Dr. Sommer is confident that "our mouse model system provides a molecular basis for the clinical findings of DiGeorge syndrome, indicating that TGF signal modulation in neural crest differentiation plays a crucial role in the etiology of this disease."

Heather Cosel | EurekAlert!
Further information:
http://www.cshl.edu

More articles from Life Sciences:

nachricht Molecular libraries for organic light-emitting diodes
24.04.2017 | Goethe-Universität Frankfurt am Main

nachricht Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Molecular libraries for organic light-emitting diodes

24.04.2017 | Life Sciences

Research sheds new light on forces that threaten sensitive coastlines

24.04.2017 | Earth Sciences

Making lightweight construction suitable for series production

24.04.2017 | Machine Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>