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 Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo

nachricht Research reveals how order first appears in liquid crystals
23.05.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Research reveals how order first appears in liquid crystals

23.05.2018 | Life Sciences

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

NIST puts the optical microscope under the microscope to achieve atomic accuracy

23.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>