Researchers Provide Study of Early Heart Development

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Researchers at The Burnham Institute for Medical Research have provided detailed insights into the early formation of the heart. A team lead by Dr. Rolf Bodmer found that two proteins, called Robo and Slit, are required for normal development of the heart and that malfunction of either of these proteins severely impacts the heart’s structure, resulting in congenital heart defects. These findings were published in the journal Current Biology released on December 20th.

Congenital heart defects involve the malformation in one or more structures of the heart or blood vessels while the fetus is developing in the uterus. According to the American Heart Association, congenital heart disease affects about 35,000 infants each year, and claims the lives of “nearly twice as many children” annually in the United States “as die from all forms of childhood cancer”. Symptoms may arise at birth, during childhood, and sometimes not until adulthood.

Working with Drosophilia melanogaster, also known as the fruitfly, the researchers showed that the Slit and Robo proteins accumulate in a specific alignment during the formation of the heart tube, a linear tube representing the primitive heart before its cells assume their rhythmical contractile functions. 

Proper alignment of the heart tube cells is critical for heart assembly and proper shape, or morphology. The researchers found that mutation or misexpression of these proteins leads to misalignment of the heart tube and results in observed heart defects.

“Although there is much interest in the understanding of the basis of heart tube assembly, little is known about the underlying molecular and genetic mechanisms that orchestrate heart development,” said Rolf Bodmer, Ph.D., Professor at the Burnham Institute for Medical Research and corresponding author in the study. “These findings provide understanding of early controls in heart development, and we are eager to conduct further studies to reveal how these controls are executed.”

Because Robo and Slit proteins are conserved in higher organisms, these discoveries may soon lead to a search for mutations in the corresponding human genes in patients with congenital heart defects, and may one day be applied to develop diagnostic tests that detect mutations in Robo and Slit for the early diagnosis of congenital heart defects.

Dr. Bodmer is known internationally for his work on the development of the heart in Drosophila. Medical scientists have long relied on fruitflies as a model for studying the genetics of embryonic development. It is now known, as Dr. Bodmer proposed a decade ago, that formation of the cardiac tube, the genesis of the heart, is a similar process in fruitflies and humans.

Li Qian and Jiandong Liu, graduate students training with Dr. Bodmer, were co-authors on this study.

This research was supported by a grant from the National Heart, Lung, and Blood Institute, and a fellowship from the American Heart Association.

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