Landmarks and Lineages in the Developing Heart

Abstract

See related article, pages 1267–1274 One of the overarching concepts underpinning mammalian embryonic development is that of “regulation.” This implies that the lineage potential of a particular cell is broader than its actual fate. Although the influential experiments in this area performed by Hans Driesch in the late 1800s concerned the fate of individual embryonic blastomeres, the concept of regulative development has pervaded all aspects of embryology, overlapping with the concept of regenerative fields. In the context of the heart, a good example is that of frog embryo cells fated to form the dorsal mesocardium and dorsal pericardial (splanchnic) mesoderm but which can “regulate” and form myocardial tissue if the normal heart is injured or extirpated.1 As we delve into the molecular mechanisms of developmental processes, we understand that limitations to cell fate are often set, particularly in the embryo, by geographical or environmental parameters, such as the source and strength of a secreted inductive signal, and these may change with time. Anatomic patterns or landmarks provide vital clues to how we should think about development and indeed disease. For example, segmentation of the embryonic paraxial mesoderm into repetitive units called somites, which bear one of the main progenitor populations for the musculoskeletal system, has been widely studied and it is known that somite segmentation is controlled by a network of synchronized molecular oscillators coupled by the Delta-Notch intercellular signaling system.2 The heart has also long been considered to have a segmental prepattern based, in part, on the series of swellings and constrictions that become evident during early heart tube formation and early fate-mapping experiments suggesting that these were the precursor structures of the chambers and their flanking regions, including the atrioventricular canal (AVC). This notion has been perpetuated as fact in embryology and medical textbooks with …