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Scientists from Gladstone Institute of Cardiovascular Disease (GICD) have followed the evolution of the four chambers of the heart in a genetic factor linked to the common development in the heart of turtles and other reptiles.
The research, published in the September 3 edition of the journal Nature, shows how a specific protein that turns on genes involved in the training center of turtles, lizards and humans.
"This is the first genetic link to the evolution of the two pumps instead of a chamber of the heart, which is an important event in the evolution of warm-blooded," said Gladstone scientist Benoit Bruneau, PhD , who led the study. "The gene, TBX5 is also involved in the disease congenital heart of man, so that our results also point to human disease to understand.
In an evolutionary standpoint, reptiles occupy a critical point in the evolution of the heart.
In the heart of birds and mammals of four rooms, frogs and other amphibians have three. "How the heart grow three fifty-seven rooms?" Bruneau said. "Various reptiles offer a continuum of three to four bedrooms. In his review, we learned a lot about how the human ventricles are normal."
He explained that, with four bedrooms, two atria and two ventricles, humans and other mammals are separated from the bloodstream into the lungs and the rest of the body, which is essential for us to be warm blooded.
When it comes to reptiles such as turtles and lizards, there is debate as to whether they have one or two rooms, pump rooms. "The main problem for us the evolution of the heart to understand the true nature of these reptiles ventricles principles to identify and understand what governs the separation of the heart in the right and left flanks," said Dr. Bruneau.
To better understand the changing hearts of reptiles, the team of Dr. Bruneau studies using modern molecular genetics TBX5. Mutations in the human gene coding for the rest of TBX5 and heart defects, particularly ventricular septal defects, the ventricular muscle wall that separates into two sections. TBX5 is a transcription factor, a protein that other genes on or off. In humans and other mammals, TBX5 levels higher in the left ventricle and in the lower right corner. The limit of high and low is exactly where it is a wall that divides the ventricle into two parts. "Based on these observations, Mr. Bruneau said," we TBX5 was a good candidate as a major player in the evolution of compartmentalization.
The team examined the distribution of TBX5 in the turtle and the green lizard. During the early stages of heart formation in both reptiles, TBX5 activity occurs during the embryonic ventricular cavity. In the lizard, which form a single ventricle, the trend remains the same as the heart develops. However, in the turtle, a primitive part of the wall separating the left and right ventricles, then the distribution of TBX5 gradually restricted to the area of the left ventricle, causing left-right gradient of activity TBX5. This means that the gradient forms TBX5 later and less intensively than in the turtle with a transparent wall, such as mammals, it is a fascinating what partitioning changed.
Dan wanted to determine whether TBX5 was truly a master regulator of the partition or a spectator. From Muizen werden Genetisch gemanipuleerde TBX5 you betuigen matig level aan een voor de ontwikkeling van het gehele hart, zoals in de harten van de schildpadden. In imitating the model of turtles, hearts of mice now seemed turtle heart. The offspring of these mice died young and had only one ventricle. This surprising result showed that a line sufficiently clear an area of secondary TBX5 is critical to the formation of a partition that separates the two ventricles induce.
"It really nailed the importance of TBX5 in heart structure to create divisions," said Dr. Bruneau.
During the development of new genetic elements of the TBX5 gene regulation that has evolved into an overt expression of TBX5. This resulted in both ventricles. Researchers are working to identify mechanisms of gene regulation in the evolution of reptiles. Work has also important implications for understanding congenital heart defects, abnormalities that are the birth of the most common, occurring in one in one hundred births in the world. Man is born with only one pumping chamber, as the heart of the frog, who suffer higher mortality and should be made wider than the newborns.
"Our study sheds new light on the evolution of the heart, which has not been reviewed more than 100 years," said Dr. Bruneau. "In a broader context, provides good support for the idea that changes in expression levels of various regulatory molecules are important in evolution. From these studies, we hope to better understand how to score defects occur in people with congenital heart disease.
Other employees of the study, Gladstone Kazuko Koshiba-Takeuchi, Alessandro D. Mori, L. Tatjana Sukonnik Bogács Kanyako and Judith Cebra-Thomas, University of Millersville, George O. Romano and Mona Nemer, the University of Montreal, Stephany Latham, Laurel Beck and Wade Michigan State University in July, R. Mark Henkelman, Hospital for Sick Children in Toronto, Eric N. Olson, University of Texas Southwestern, Scott F. Gilbert, Swarthmore College, Jun Takeuchi, Tokyo Institute of Technology, and Brian L. Black, University of California at San Francisco.
The study was supported by the March of Dimes, William H. Young, Jr., NIH, National Science Foundation, University of Toronto, Fumi Yamamura, Sumitomo and the Nakajima Foundation, the Heart and Stroke Foundation of Canada and the Canadian Institutes of Health Research.
Benoit Bruneau primary connection with the Gladstone Institute of Cardiovascular Diseases, the youngest of whom was William H., Jr., a researcher, where all the laboratory and its research is conducted. It is also an associate professor of pediatrics at the University of California at San Francisco.
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