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!
Atomic-level motion may drive bacteria's ability to evade immune system defenses
24.04.2017 | Indiana University
Two-dimensional melting of hard spheres experimentally unravelled after 60 years
24.04.2017 | University of Oxford
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...
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...
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...
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...
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...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences