Mutant gene causes heart malformations.

In the very early days of development, some cells in the human embryo migrate to the right and others travel to the left. Those that end up on the right are destined to become organs such as the liver. Those that move to the left will specialize to become the heart, stomach, and other left-sided organs.

For cells that will become the heart, reaching the proper position in the body is critical. If cells take a wrong turn, the heart will develop abnormally. Babies born with such cardiac misplacements often die or require extensive surgery.

But what gives primitive cells a road map to their proper destination? Researchers at Yale University School of Medicine believe that a gene and its protein product may act as traffic cops, directing cells that will become heart cells to swing to the left.

Donna Rounds, Martina Brueckner, and their coworkers have been studying a mutant gene that causes a misplacement of the heart in mice. Their research suggests this gene lies along a particular region of mouse chromosome 12. The Yale team is currently trying to isolate and analyze that mutant mouse gene.

At the same time, the Yale group is trying to unravel the human side of the heart-defect story. They suspect the human version of this gene lies on chromosome 14. The researchers are now in the process of studying families that have a history of this heart condition, Rounds says.

Once the researchers home in on the human gene, they can begin the process of analyzing its protein, she says. This protein may somehow signal embryonic cells to turn left instead of right, she speculates.

Studies such as this could help answer questions about the first few weeks of embryonic life and perhaps give scientists clues to uncovering the secrets of other genes associated with congenital heart disease, the researchers add.