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Why is the heart pear-shaped?

T.V. Jayan explains, with the help of a new study:  It’s often been said that there is no engineer quite like Mother Nature. A living organism ” with all its parts that fit in so smoothly  is after all an engineering marvel. But this near-perfect  manufacturing  skill of Nature has often fanned the debate on whether life was created, or evolved.

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If the advocates of creationism are ready to swallow, however grudgingly, the theory that life originated from the amoeba eons ago, science has not been able to give convincing answers to a number of sub-questions. How does, for instance, a tiny, fragile fertilised egg grow into a body of full-blown organs without any “external” guidance? Why are the shapes of organs in a human being as they are? Why are our legs longer than our arms?

Ardent proponents of evolutionary biology, however, may no longer have to fumble for answers to many such questions. A team of scientists from the Skirball Institute of Biomolecular Medicine, affiliated to the New York University School of Medicine, recently proved that logic could explain some of these difficult questions. Led by Deborah Yelon, the scientists unravelled the factors governing the complex process of the formation of the heart, which is a simple tube in early development, growing into a four-chambered, intricate organ with a characteristic pear shape. The researchers published their study in the February 20 issue of PLoS (Public Library of Science) Biology.

The heart, like many other organs, undergoes dramatic changes in its three-dimensional form as the embryo develops and functional demands intensify. Before it becomes a multi-chambered organ, it exists as a simple tube made up of myocardium (muscle) lined by endocardium (endothelium). As this thin-walled tube bulges outward, the chambers emerge and eventually acquire the characteristic dimensions of curvature and thickness.

In an article in Current Biology (September 2005), Sheffield University scientist David Strutt wrote that in order to control the shape and size of an organ, it is necessary that the dimensions be measured as the organ grows, and growth stops in each axis at the appropriate time.

But how this is achieved largely remains a mystery.

Developing organs acquire a specific three-dimensional form that ensures their normal functioning. The unique shape of the heart in higher-order animals, too, is critical for proper functioning. It is composed of a series of chambers that rhythmically drive blood circulation. Each of the chambers is designed for its optimal functional capacity. The organ, which commences beating from approximately 21 days of conception, is responsible for pumping blood via blood vessels through repeated, rhythmic contractions. In the process, it picks up carbon dioxide from the blood and drops it off in the lungs in exchange for oxygen which is in turn circulated through the blood.

Organs acquire their characteristic shapes not simply as a consequence of the accumulation of cells that profusely divide and multipl  Shape is also a physical process during which tissues are pressed, pulled and moved,  the scientists said.

In the experiments using transgenic (containing genes transferred from another species) zebra fish in which individual cardiac cells can be watched, Deborah Yelon, her student Heidi Auman and others demonstrated that cells change size and shape, enlarging and elongating to form bulges in the heart tube and eventually the chambers. The big question was whether the function of the heart — that is, blood flow — too influences cell shape.

Their studies using zebra fish   genetically modified so that each fish has a functional defect — helped them to find out that both blood flow and contraction of the cardiac tissues play a role in shaping cardiac cells. The unique tools the researchers used helped to clearly show that blood flow affects form. Further, they could define this at the cellular level.

The contribution of individual cell morphology to the overall shape was not previously shown, particularly in relation to the impact on chamber morphogenesis (formation and shape), said Deepak Srivastava, director of the Gladstone Institute of Cardiovascular Disease, University of California, San Francisco.

“This is an important advance as although it has long been thought that blood flow does affect morphogenesis, the two have been difficult to isolate in a cause-and-effect manner,” Srivastava told KnowHow.

Moreover, the work is more rigorous and detailed than previous such exercises, he said.

However, Larry Taber, professor of biomedical engineering at Washington University, feels that the researchers are missing some key points. For example, he says, they talk about curvature (of the heart chambers) but never explicitly discuss looping, which causes the greatest changes during heart development. Looping, it may be mentioned, involves the bending and twisting of the heart tube to create asymmetry of the chambers as is required for optimal functioning.

There are a lot of misconceptions about looping among developmental biologists, including some propagated in this paper,  Taber, who has been studying heart formation in chicks for a couple of decades, told KnowHow.

He, however, said that the Skirball team’s conclusion that contraction and blood flow are important for chamber expansion seems plausible. He also said that cell shape changes can cause curvature changes as well. What he disagrees with is their implication that contraction and blood flow regulate looping.

The use of zebra fish with minor induced genetic defects helped the Skirball Institute scientists to show that slight abnormalities in cell morphology may lead to substantial changes in the shape and functioning of the cardiac chambers. This could probably explain aberrations observed in some types of heart disease.

Source:The Telegraph (Kolkata,India)

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