Gene Orchestrates Heart Chamber Development

February 19, 1998--Early in development, the vertebrate heart is transformed from a narrow tube into a powerful four-chambered pump. Researchers have now found a gene that influences formation of the chambers of the heart. The discovery also provides a new set of tools to probe how this crucial developmental step occurs.

Zheng-Zheng Bao, a postdoctoral fellow in HHMI investigator Constance Cepko's laboratory at Harvard Medical School, identified Irx4 (for iroquois-related homeobox gene), a gene expressed only in the ventricles of embryonic chicken hearts. "This is the first gene that is the right type and is expressed early enough to play a key regulatory role in setting up the chambers," Cepko says. She and her colleagues published their research in the February 19, 1999, issue of the journal Science.

All vertebrate hearts have two types of chambers -- atria and ventricles, which pump blood into and away from the heart, respectively. In vertebrate embryos, the developing heart first resembles a tiny tube, which folds into four chambers as it grows. "How these different chambers form during development is not known," says Cepko.

Heart muscle in the atria and ventricles has different contractile properties that can be traced to different forms of the protein myosin. In an attempt to understand the early stages of cardiac development, researchers have mapped the expression patterns of the myosin proteins. They know that atrial myosin heavy chain-1 gene (AMHC1) is expressed only in the atria, for example, while the ventricle myosin heavy chain-1 gene (VMHC1) is restricted to the ventricles. It has not been clear how expression of these genes is restricted to one chamber or the other, Cepko says.

A developmental neuro

Contact: Jim Keeley
Howard Hughes Medical Institute

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