Hearts Or Tails? Genetics Of Multi-chambered Heart Evolution

Brad Davidson and colleagues in Michael Levine's lab at UC Berkeley have discovered that the transcription factor Ets1/2, along with the signaling molecule FGF, controls early heart formation in the sea squirt, Ciona intestinalis.

Sea squirts are most commonly found in shallow ocean waters attached to algae, rocks or seaweed. They have been used for over 100 years as a highly useful experimental model organism for the study of animal development. A simple chordate, Ciona is being used in the lab to study the heart development of higher organisms because it shares several characteristics with vertebrates - although ultimately, Ciona, develops a heart with just one chamber (as opposed to vertebrates' multi-chambered heart).

All of the cells that form the Ciona heart are originally derived from two early embryonic cells (called bastomeres). These cells divide into separate lineages: the smaller rostral cells become heart muscle, while the larger caudal cells become tail muscle. Davidson and colleagues found that Ets1/2 underlies the cells' decision to become either heart or tail. When activated, Ets1/2 instructs cells to form heart muscle.

When the scientists blocked Ets1/2 activity (either by inhibiting the Ets1/2 gene, itself, or its upstream modulators), Ciona heart specification was likewise blocked. Alternatively, the over-expression of Ets1/2 in caudal cells caused the cells to switch their fate from tail to heart.

The expanded cardiac field in Ets1/2-activated mutants results in a proportion of animals having a functional, two-chambered heart. "The conversion of a simple heart tube into a complex heart was discovered by chance, but has general implications for the evolutionary origins of animal diversity and complexity", says Mike Levine, a co-author of the paper.