Clonally dominant cardiomyocytes direct heart morphogenesis

Abstract

As vertebrate embryos develop to adulthood, their organs dramatically increase size and change tissue architecture. Here, we used a multicolor clonal analysis to define contributions of many individual cardiomyocytes as the zebrafish heart undergoes morphogenesis from a primitive embryonic structure into its complex adult form. We find that the single cardiomyocyte-thick wall of the juvenile ventricle forms by lateral expansion of several dozen cardiomyocytes into muscle patches of variable sizes and shapes. As juveniles mature into adults, this structure becomes fully enveloped by a new lineage of cortical muscle. Adult cortical muscle originates from a small number (~8) of cardiomyocytes that display clonal dominance reminiscent of stem cell populations. Cortical cardiomyocytes initially emerge from internal myofibers that in rare events breach the juvenile ventricular wall and expand over the surface. Our study illuminates dynamic proliferative behaviors that generate adult cardiac structure, revealing clonal dominance as a key mechanism that shapes a vertebrate organ.