Patterns of myocardial histogenesis as revealed by mouse chimeras

In order to study the pattern of clonal myocyte distribution during mammalian heart development, we have exploited embryo aggregation chimeras using, as cellular markers, an enhanced jellyfish green fluorescent protein (eGFP) transgene and a desmin-promoter-driven, nuclear-localized beta-galactosidase (nlacZ) knock-in. In neonatal, weanling, and adult chimeric atria and ventricles, irregularly formed patches of various sizes rather than highly dispersed cardiomyocytes were observed. Most of the smaller patches and single cardiomyocytes were found in spatial neighborhood of large patches. This indicated largely coherent clonal growth during myocardial histogenesis combined with tangential displacement or active migration of myocytes. The patterns of ventricular walls were simpler than those of the septum and the atria. In the adult heart, large myocardial volumes devoid of eGFP-positive cardiomyocytes indicated a lack of secondary immigration of blood-borne stem cells into the myocardium. The patterns of oligoclonal expansions revealed in this work might be helpful in detecting and analyzing cell-lineage-based pathological processes in the heart.