DAVIDSON, Brad; SHI, Weiyang; LEVINE, Michael; UC Berkeley; UC Berkeley; UC Berkeley: Origins of the Chordate Heart

Prevailing models of vertebrate/arthropod heart development focus on a conserved network of BMP signaling molecules and GATA-4 and Nkx-2.5 transcription factors functioning during gastrulation. There is mounting evidence for an earlier specification event in vertebrates, although the underlying mechanism remains obscure. In mouse and the basal chordate, Ciona savignyi, the bHLH transcription factor Mesp is expressed in the heart field prior to gastrulation, where it is essential for migration of cardiac progenitors. A detailed analysis of Mesp regulation indicates that restricted expression depends on spatially localized expression of the T-box transcription factor Tbx-6c. Subsequently, the Mesp expressing blastomeres form two distinct lineages in Ciona tadpoles: the heart rudiment and anterior tail muscles. Expression of a hyper-activated form of Mesp can transform the anterior tail muscle into heart tissue, resulting in the formation of a second beating heart. Thus, Mesp activity does not simply induce proper cell migration, but instead functions as a cardiac determinant that can induce heart differentiation without migration. There is every indication that the Mesp pathway is conserved in vertebrates, but not in non-chordates such as Drosophilae. The characterization of the earliest steps of chordate heart specification alter the current view of heart evolution, suggesting that conserved aspects of chordate/arthropod heart development are superimposed on highly divergent methods of initial cardiac specification.