Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gladstone scientists find first genetic link between reptile and human heart evolution

03.09.2009
Turtles and other reptiles offer clues to the development of 4 chambers and to congenital heart disease

Scientists at the Gladstone Institute of Cardiovascular Disease (GICD) have traced the evolution of the four-chambered human heart to a common genetic factor linked to the development of hearts in turtles and other reptiles.

The research, published in the September 3 issue of the journal Nature, shows how a specific protein that turns on genes is involved in heart formation in turtles, lizards and humans.

"This is the first genetic link to the evolution of two, rather than one, pumping chamber in the heart, which is a key event in the evolution of becoming warm-blooded," said Gladstone investigator Benoit Bruneau, PhD, who led the study. "The gene involved, Tbx5, is also implicated in human congenital heart disease, so our results also bring insight into human disease."

From an evolutionary standpoint, the reptiles occupy a critical point in heart evolution.

While bird and mammalian hearts have four chambers, frogs and other amphibians have three. "How did hearts evolve from three to four chambers?" Bruneau said. "The different reptiles offer a sort of continuum from three to four chambers. By examining them, we learned a lot about how the human heart chambers normally form."

He explained that with four chambers—two atria and two ventricles—humans and all other mammals have completely separate blood flows to the lungs and to 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 about whether they have one or two ventricles, which are the pumping chambers. "The main question for us to understand the evolution of the heart was to identify the true nature of these early reptile ventricles and to figure out what controls the separation of the heart into left and right sides," said Dr. Bruneau.

To better understand reptile heart evolution, Dr. Bruneau's team used modern molecular genetics to examine Tbx5. Mutations in the human gene that encodes Tbx5 result in congenital heart disease and, in particular, defects in the ventricular septum, the muscular wall that separates the ventricle into two sections. Tbx5 is a transcription factor, a protein that turns other genes on or off. In humans and other mammals, Tbx5 levels are high in the left ventricle and low in the right. The boundary of high and low levels is right where the septum forms to divide the ventricle into two parts. "Based on these observations," said Dr. Bruneau, "we thought Tbx5 was a good candidate as a key player in the evolution of septation."

The team looked at Tbx5 distribution in the turtle and the green anole lizard. During the early stages of heart formation in both reptiles, Tbx5 activity is found throughout the embryonic ventricular chamber. In the lizard, which forms only one ventricle, this pattern stays the same as the heart develops. However, in the turtle, which has a primitive septum that partially separates the ventricles into left and right sides, distribution of Tbx5 is later gradually restricted to the area of the left ventricle, resulting in a left-right gradient of Tbx5 activity. This meant that the gradient of Tbx5 forms later and less sharply in the turtle than in species with a clear septum, such as mammals, providing a tantalizing clue about how septation evolved.

They then wanted to determine whether Tbx5 was really a main regulator of septation or merely a bystander. Mice were genetically engineered to express Tbx5 at a moderate level throughout the developing heart, just like in turtle hearts. By mimicking the turtle pattern, mouse hearts now resembled turtle hearts. The offspring from these mice died young and had only a single ventricle. This striking result conclusively showed that a sharp line delineating an area of high level of Tbx5 is critical to induce formation of a septum between the two ventricles.

"This really nailed the importance of Tbx5 in patterning the heart to allow septation to occur," said Dr. Bruneau.

During evolution, new genetic regulatory elements evolved to tell the Tbx5 gene to form a sharp boundary of Tbx5 expression. This resulted in two ventricles. Researchers will now work to identify those genetic regulatory mechanisms during the evolution of reptiles. The work also has important implications for the understanding of congenital heart defects, which are the most common human birth defect, occurring in one out of every one hundred births worldwide. Humans born with only one pumping chamber, resembling frog hearts, suffer the highest mortality and require extensive surgery as newborns.

"Our study provides exciting new insights into the evolution of the heart, which had not been examined in over 100 years," Dr. Bruneau explained. "In a larger context, it provides good support for the concept that changes in the expression levels of various regulatory molecules are important in evolution. From these studies we also hope to understand further how defects in septation occur in humans with congenital heart disease."

Other contributors to the research were Gladstone's Kazuko Koshiba-Takeuchi, Alessandro D. Mori, Bogac L. Kanyak and Tatyana Sukonnik; Judith Cebra-Thomas of Millersville University, Romain O. Georges and Mona Nemer of the University of Montreal; Stephany Latham, Laurel Beck and Juli Wade of Michigan State University; R. Mark Henkelman, Hospital for Sick Children, 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, San Francisco.

The study was supported by the March of Dimes, William H. Younger, Jr., the NIH, the National Science Foundation, the University of Toronto, the Fumi Yamamura Foundation, the Sumitomo and Nakajima Foundations, the Heart and Stroke Foundation of Canada and the Canadian Institutes for Health Research.

Benoit Bruneau's primary affiliation is with the Gladstone Institute of Cardiovascular Disease where he is the William H. Younger, Jr. Investigator, and where his laboratory is located and all of his research is conducted. He is also Associate Professor of Pediatrics at the University of California, San Francisco.

About the Gladstone Institutes

The J. David Gladstone Institutes, an independent, nonprofit biomedical research organization, affiliated with the University of California, San Francisco, is dedicated to the health and welfare of humankind through research into the causes and prevention of some of the world's most devastating diseases. Gladstone is comprised of the Gladstone Institute of Cardiovascular Disease, the Gladstone Institute of Virology and Immunology and the Gladstone Institute of Neurological Disease. More information can be found at www.gladstone.ucsf.edu.

Valerie Tucker | EurekAlert!
Further information:
http://www.gladstone.ucsf.edu

More articles from Life Sciences:

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

nachricht How protein islands form
15.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

Im Focus: Scientists improve forecast of increasing hazard on Ecuadorian volcano

Researchers from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, the Italian Space Agency (ASI), and the Instituto Geofisico--Escuela Politecnica Nacional (IGEPN) of Ecuador, showed an increasing volcanic danger on Cotopaxi in Ecuador using a powerful technique known as Interferometric Synthetic Aperture Radar (InSAR).

The Andes region in which Cotopaxi volcano is located is known to contain some of the world's most serious volcanic hazard. A mid- to large-size eruption has...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New thruster design increases efficiency for future spaceflight

16.08.2017 | Physics and Astronomy

Transporting spin: A graphene and boron nitride heterostructure creates large spin signals

16.08.2017 | Materials Sciences

A new method for the 3-D printing of living tissues

16.08.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>