Commentary on “The precardiac areas and formation of the tubular heart in the chick embryo” by Stalsberg and DeHaan 1969

Developmental biologists, like fans of superhero legends, love a good origin story. It’s captivating to follow our favorite cells as they arise from their humble beginnings to attain their fantastic destinies, and it’s intriguing to consider how their paths were shaped by the environments encountered en route. Fate mapping approaches, in which cells are marked in the early embryo and then later detected once they reside in a particular tissue, reveal the beginning and end of a developmental story and allow us to formulate hypotheses regarding the trajectories followed in between. Moreover, fate map data can inspire models for the regulatory mechanisms that direct uncommitted cells toward their ultimate destinations.

Fifty years ago, many developmental biologists were eagerly applying classical fate mapping techniques in an effort to understand the cellular underpinnings of pattern formation within a variety of embryonic organs. This approach, and its value, is admirably exemplified by the work of Stalsberg and DeHaan (1969), who focused on the fate map of the precardiac mesoderm in the chick embryo. Prior studies had identified a pair of bilateral “heart-forming areas” in the early chick embryo, and Stalsberg and DeHaan aimed to acquire a refined understanding of their dimensions and organization. Importantly, they wanted to determine where the precursors of different sections of the heart, such as the conus, ventricle, and atrium, resided within these bilateral areas. Were distinct subsets of precursors strictly organized or frequently intermingled? Detection of a pattern within the precardiac mesoderm would have interesting implications for the morphogenetic manner through which the bilateral fields of precursors become an organized organ at the embryonic midline.

To construct their fate map, Stalsberg and DeHaan chose to transplant small squares of tissue from various locations in radiolabeled donor embryos into the equivalent positions of unlabeled host embryos at stage 5. The next day, when the embryos had reached stage 12, they evaluated the positions of the transplanted cells, relative to a carefully defined atlas of 24 subregions within the heart tube. By comparing the initial and final sites of each transplant, they concluded that the precursors of distinct regions of the heart are relatively organized within the precardiac mesoderm, with a general correspondence between the rostrocaudal axis of the heart tube and the positions of the precursors. This organization of the cardiac fate map suggested that cardiac morphogenesis might proceed in a highly coherent fashion, without much intermixing of the myocardial precursors. Indeed, additional work performed by Stalsberg and DeHaan – including systematic microdissection and sectioning of the mesoderm, as well as tracking embedded iron oxide particles over time – suggested that the precardiac mesoderm behaves as a cohesive sheet of tissue throughout the process of heart tube formation.

Collectively, the work of Stalsberg and DeHaan, together with other contemporaneous fate mapping efforts, provided a fundamental framework for envisioning cardiac morphogenesis as an orderly process in which an organized sheet of precursors “condenses, stretches, folds, and deforms” to give rise to a patterned heart tube. Over the following decades, as techniques for fate mapping and lineage tracing have become increasingly sophisticated, the field has continued to build on this foundation, both by reinforcing the primary message regarding early patterning of the precardiac mesoderm and by enhancing our understanding of the diversity of cardiac lineages and the complexity of their organization (Evans et al., 2010; Meilhac and Buckingham, 2018). Additionally, the advent of a variety of strategies for high-resolution imaging have provided new opportunities to track cardiac cell behavior and to evaluate its regulation by intrinsic properties of the mesoderm as well as external influences of neighboring tissues (Cortes et al., 2018; Varner and Taber, 2012). Even so, many mysteries remain regarding the molecular mechanisms that direct cardiac cell fate and control the coherence of cardiac morphogenesis. Thus, the classic experiments of Stalsberg and DeHaan still resonate today, as we continue to seek the regulatory principles that underlie their “unified concept of heart formation and tubulation”.