Just as the emotions it represents are dynamic, the heart's development requires dynamic shifts in proteins that prompt alternative spicing, a mechanism that allows a given gene to program the cell to make several proteins, said a group of researchers at Baylor College of Medicine in a report that appears online in the journal Proceedings of the National Academy of Sciences.
Using a technique called splicing sensitive microarrays or gene chips that help identify genes, the researchers from BCM, Massachusetts Institute of Technology in Cambridge and Rosetta Inpharmatics, LLC in Seattle identified two proteins (CUGBP and ETR-3-like factors called CELF and muscleblind-like protein called MBNL1) that reprogram alternative splicing in the developing hearts of mice, affecting how the heart grows during the pre-birth, immediately post-birth periods.
There is a rapid decrease in the amount of CELF proteins (more than 10-fold) and a concomitant increase in MBNL1 proteins (nearly 4-fold) during the first two weeks after birth. The finding has implications for a muscle-wasting ailment called myotonic dystrophy as well as for normal heart development.
"These are physiologically important times," said Dr. Thomas Cooper, professor of pathology and molecular and cellular biology at BCM and the senior author of the report. "Before birth, the heart is getting ready for a complete change in function. After birth, it needs to work harder to accommodate the demands of moving about."
"It is now clear that there's a new level of regulation during development," he said. "It's not just turning genes on and off. It is changing the composition of the proteins expressed from this one set of genes."
In fact, half of the alternative splicing changes that occur during heart development are controlled by the CELF and muscleblind-like factors, said Cooper.
Most of the changes in alternative splicing found in mouse heart development were also found in chicken heart development strongly suggesting that the changes are very important for normal heart. It is very likely that the same changes are needed for normal human heart development as well.