A particular gene, called Gata5, acts in concert with a related gene to regulate early heart development in animals, researchers have found in a genetic study.
The study, led by Dr. Peter J. Gruber, a cardiothoracic surgeon at The Children's Hospital of Philadelphia, contributes to understanding how the earliest stages of heart development may go awry, resulting in congenital heart defects in humans.
Advertisement"We uncovered a role for the Gata5 gene, a role that has been unappreciated in vertebrate cardiac development. Gata5 is a gene that is essential to heart development in other animals, such as frogs and zebrafish, but contrary to expectations, deleting this gene seemed to have no effect on the hearts of mammals. We found, however, that in mice, this gene cooperates closely with other genes to affect heart development. It may work similarly in humans," said Gruber.
The Gata5 gene expresses the protein GATA5, which is a member of a family of zinc-finger transcription factors-proteins that act as switches to turn gene activity on or off.
The GATA transcription factors carry out important tasks during an organism's development.
In the study on mice, the researchers genetically engineered mice in which Gata5 genes were inactive, and found the animals were healthy, with normally functioning hearts.
However, they found that those mice showed increased expression of another gene in the same family, Gata4, which suggested that Gata4 might compensate for the loss of Gata5.
When they bred a new group of mice in which Gata5 was inactive and had only one functioning Gata4 allele (each gene has two alleles) those mice all had profound cardiac defects and died before birth.
"Our research suggests that Gata5 has a previously unsuspected role during cardiac development, acting cooperatively with Gata4 to direct the heart to form normal structures," said Gruber.
"If the same process occurs in humans, that tells us something new about prenatal heart development. The research also shows that studying a single gene in isolation may not be sufficient. Here one gene buffers the effects of losing another gene," he added.
"Although a long way off, greater understanding of biological mechanisms during early heart development may eventually provide useful targets for more accurate diagnosis or personalized treatment of children with congenital heart disease," added Gruber.
The study has been published in the latest issue of the Journal of Biological Chemistry.