Of Fish and Men
Clonal Lineage Analysis Identifies Divergence in Myocardial Development
Clonally Dominant Cardiomyocytes Direct Heart
Gupta and Poss
A clear understanding of myocardial development is essential not only for understanding the molecular basis of congenital heart disease and its prevention, but also for successful regeneration after cardiac injury. A recent study used a novel Cre/LoxP-based lineage-tracing approach with a multicolor reporter in zebrafish to examine the fates of populations of developing cardiomyocytes. The results showed that a remarkably few number of clones of cardiomyocytes are involved in the formation of adult zebrafish heart. Furthermore, a striking difference in the mechanism of myocardial compaction was described, involving the creation of a completely new layer of cortical myocardium.
Cardiac development is a complex process involving multiple, meticulously orchestrated molecular, cellular, and morphogenetic events to give rise to a properly functioning organ. Although detailed investigation in model organisms such as flies, frogs, chicks, and mice have greatly informed our understanding of the early regulators in this process, there has been a relative lack of data addressing the later stages of myocardial formation and the cell origins that give rise to maturing cardiomyocytes.
To identify the native myocardial architecture, pioneering studies from Mikawa et al have attempted to clonally label myocardial cell populations during cardiac development in the chick by using a single-cell retroviral tagging strategy (Figure).1 These studies showed that one single-labeled cardiomyocyte can give rise to a wedge-shaped cluster of descendent cardiomyocytes that migrate inward from the outer subepicardial layer toward the inner trabecular layer. It was proposed that each of these cell clusters represent individual units of clonally related myocardium that function in synchrony.2 Consistent with this model, the development of the trabecular myocardium in mice appears to involve the delamination of myocardial cells away from their neighbors along the epicardial wall, a cell population that eventually gives rise to the compact myocardial layer (Figure). …