Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study finds protein that plays key role in early embryonic development

13.05.2010
Research sheds light on prenatal heart formation, chromosome 22q.11 deletion syndrome

Researchers studying the common genetic disorder chromosome 22q.11 deletion syndrome have identified key proteins that act together to regulate early embryonic development. One protein is essential to life; in animal studies, embryos without the protein do not survive past the first few days of gestation.

Although the findings do not currently affect treatments for chromosome 22q.11 deletion syndrome, they shed light on the biological events that give rise to the syndrome, which often includes congenital heart defects. They also reveal the previously unsuspected importance of one protein in the earliest stages of development.

"The heart is among the first organs to develop in humans and other mammals," said neonatologist Jason Z. Stoller, M.D., of The Children's Hospital of Philadelphia, corresponding author of the study, appearing online today in the May issue of the journal Experimental Biology and Medicine. Stoller collaborated with Jonathan A. Epstein, M.D., scientific director of the Penn Cardiovascular Institute at the University of Pennsylvania, and senior author of the study.

Chromosome 22q.11 deletion syndrome, also known as DiGeorge syndrome, is the most common human disorder caused by a missing chromosome region, occurring at least once in 4,000 live births. It can vary in severity, but may affect many parts of the body, with symptoms including heart defects, immune and endocrine problems, cleft palate, gastrointestinal conditions, growth delay and neuropsychiatric abnormalities. The 22q and You Center at Children's Hospital is an international leader in clinical care and research in this syndrome, providing multidisciplinary evaluation and treatment for hundreds of patients from over 40 states and 15 countries.

Because of structural instability in a portion of chromosome 22, one region may be deleted, typically containing 30 genes. One of those genes, TBX1, holds the genetic code for a type of protein called a transcription factor—which regulates other genes. In 2005, Stoller and Epstein found that within this protein, also called TBX1, a particular domain was crucial and played a key role in chromosome 22q.11 deletion syndrome.

The current study, said Stoller, aimed to discover proteins that interact with the Tbx1 protein and to identify some of the biological events that give rise to chromosome 22q.11 deletion syndrome. The study team identified the protein Ash2l as an important partner of Tbx1. "The two proteins act together to influence other genes that may impair biological systems affected in the deletion syndrome," said Stoller. "Ash2l is important in epigenetics—changes in gene activity that do not involve alterations to the genetic code spelled out in DNA." In epigenetic processes, chemical groups attached either to DNA, or to DNA-associated proteins called histones, switch gene activity on or off.

Many other steps resulting from this protein interaction have yet to be discovered, to determine how these molecular events cause specific effects, such as cleft palate or abnormalities in the thymus gland that occur in chromosome 22q.11 deletion syndrome. Said Stoller, "As with much research in basic science, discovering gene pathways and biological mechanisms may lay the foundation for future development of drugs or other therapies to act on these pathways, but such clinical applications are still in the future."

Another finding in the current study does not directly affect patients with the deletion syndrome, but shows that the Ash2l protein is absolutely essential to normal development. Mice that were bred to lack the gene for Ash2l produced embryos that, without exception, died very early in gestation. "The fact that this protein is necessary to early embryonic survival suggests that Ash2l regulates many genes during the early stages of development," said Stoller.

The National Institutes of Health provided funding support for this study. Co-authors with Stoller and Epstein were from the University of Pennsylvania School of Medicine; Mount Sinai School of Medicine, New York City; the University of California Los Angeles; and Huagene Biosciences of Fujian, China.

"Ash21 interacts with Tbx1 and is required during early embryogenesis," Experimental Biology and Medicine, May 2010, published online May 12, 2010. doi:10.1258/ebm.2010.009318

About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 460-bed hospital recognition as a leading advocate for children and adolescents.

John Ascenzi | EurekAlert!
Further information:
http://www.chop.edu

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Biocompatible 3-D tracking system has potential to improve robot-assisted surgery

17.02.2017 | Medical Engineering

Real-time MRI analysis powered by supercomputers

17.02.2017 | Medical Engineering

Antibiotic effective against drug-resistant bacteria in pediatric skin infections

17.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>