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OutFoxed! New research may redefine late-stage cardiac development

(Philadelphia, PA) -- According to the American Heart Association, congenital cardiovascular defects, such as congenital heart disease (CHD), are present in about one percent of live births and are the most common malformations in newborns. A team of University of Pennsylvania School of Medicine researchers, led by Edward E. Morrisey, PhD, Associate Professor of Medicine, have been investigating how the heart develops from its earliest stages of development to its late stages, with the hope of learning why some hearts don't develop correctly. Dr. Morrisey's latest finding to be published in the September 10th issue of Science may redefine current models of how the heart develops in mammals. "Understanding the earliest steps in heart development gives us insight into the possible genetic causes of the dramatic heart defects exhibited by so many newborn babies, " says Morrisey.

During normal embryonic development in mammals, pre-cardiac cells form the bilateral cardiac primordia two symmetrical, tube-shaped regions located on both sides of the early embryo. As cardiac development progresses, these two regions fuse, forming one large tube, which, in turn, further develops into the four-chamber heart.

Using genetically engineered mice, Penn researchers successfully inactivated the Foxp4 binding protein, which resulted in the inability of the bilateral tubes to fuse. They found that each region of pre-cardiac cells still developed into a single tube, and then further developed into a four-chamber heart. This resulted in the mouse embryos developing two, four-chambered hearts exhibiting most aspects of advanced heart development. Eventually these embryos succumbed due to the lack of correct blood flow with two hearts pumping into the same set of blood vessels.

Foxp4 belongs to a class of DNA binding proteins called transcription factors that turn other genes on and off. Interestingly, Foxp4 is not expressed in heart muscle cells themselves b
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Contact: Ed Federico
ed.federico@uphs.upenn.edu
215-662-2560
University of Pennsylvania School of Medicine
9-Sep-2004


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