Most people think the development of the heart only happens in the womb, however the days and weeks following birth are full of cellular changes that play a role in the structure and function of the heart.
Using mouse models, researchers at Baylor College of Medicine have now been able to categorize the alternative splicing (the process in which genes code proteins, determining their role) that takes place during these changes and what mechanisms they affect.
The findings, which appear in Nature Communications, also helped to identify a protein that regulates some of the alternative splicing and then goes on to change dramatically in its expression during the postnatal period.
"The cells of the heart stop dividing after birth but they have to continue growing and working together for the heart to pump the blood. So basically, we have made the connection between the process of alternative splicing and the development of this system that coordinates heart contraction and function," said Thomas Cooper, the S. Donald Greenberg professor of pathology & immunology at Baylor.
Researchers were able to separate two main cell types of the mouse heart, the cardiomyocytes and cardiac fibroblasts. Using RNA sequencing they looked at early- and late-stage development within the days following birth. RNA sequencing is a technique that reveals the messages transmitted to the cell from the genome, allowing researchers to see the mechanisms associated with gene expression. During the sequencing, Cooper and his colleagues were able to see what genes are turned on and off and which ones undergo an alternative splicing change.
By pinpointing these changes, the team of researchers identified the CELF1 protein as being responsible for regulating certain alternative splicing events, Cooper said. So by turning on and off CELF1 expression at different points in development, researchers were able to see how the protein affects development during this stage.
"We looked at hundreds of genes that undergo alternative splicing and were able to see which ones are regulated by CELF1," Cooper said. "We asked if is there anything in common among these genes and found that some were responsible for endocytosis and vesicular trafficking. So what is going on in heart development that is related to these processes associated with cell membrane dynamics?"
It turns out, Cooper said, that the cell membrane machinery that is required to coordinate contraction, the electrical activity of the heart, all develops in this postnatal period.
There are some ailments that CELF1 is associated with such as arrhythmias and some forms of muscular dystrophy and Cooper said it is possible that this protein could provide a treatment target.
"Now we know what happens during this period in terms of what genes are on and off and what alternative splicing takes place. This is new information for further studies to build on," he said. "There is still information about this developmental stage that must be looked at first."
This work was performed by Jimena Guidice, a postdoctoral fellow in Cooper's lab. Others who contributed to this research include Zheng Xia, Marissa A. Scavuzzo, Amanda J. Ward, Auinash Kalsotra, Wei Wang, Xander H.T. Wehrens, Wei Li, all of Baylor College of Medicine; and Eric T. Wang and Christopher B. Burge, both with Massachusetts institute of Technology. Ward and Kalsotra are currently with Isis Pharmaceuticals, Carlsbad California.
Funding for this research is from the National Institutes of Health (R01HL045565, R01AR060733, and R01AR045653), the Muscular Dystrophy Association, the Pew Charitable Trusts, the Myotonic Dystrophy Foundation, the American Heart Association, the National Institute of Neurological Disorders and Stroke, CPRIT and Foundation Leducq.
Graciela Gutierrez | Eurek Alert!
New mechanisms uncovered explaining frost tolerance in plants
26.09.2016 | Technische Universität München
Chains of nanogold – forged with atomic precision
23.09.2016 | Suomen Akatemia (Academy of Finland)
The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.
“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...
With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.
Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...
For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.
Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...
At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.
In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...
Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.
K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...
23.09.2016 | Event News
20.09.2016 | Event News
16.09.2016 | Event News
26.09.2016 | Materials Sciences
26.09.2016 | Materials Sciences
26.09.2016 | Materials Sciences