Regulation of heart morphology: current molecular and cellular perspectives on the coordinated emergence of cardiac form and function

Abstract

Background: During early heart development, in addition to cells being induced to differentiate into cardiomyocytes, pathways are activated that lead to cardiac morphogenesis or the development of form.

Methods: Orchestration of organogenesis involves the incremental activation of regulatory pathways that lead to pivotal transition points, such as cardiac compartment delineation and looping. Each embryonic stage sets up the correct patterning of morphoregulatory molecules that will regulate the next process, until an organ is formed from the mesoderm layer after gastrulation. The current review provides an understanding of the morphoregulatory, cell adhesion and extracellular matrix-mediated, processes that coordinate development of heart form with that of function. The period reviewed encompasses the formation of a definitive cardiac compartment from the lateral plate mesoderm to the time-point in which the single, beating heart tube loops directionally to the right. Looping results in the correct spatial orientation for subsequent modeling of the four-chambered heart. Even subtle alterations in looping can form the basis upon which malformations of the inlet or the outlet regions of the heart, or both, are superimposed.

Results: In the future, DNA microarray data sets may allow modeling the specific sequence of gene regulatory dynamics leading to these transition points to discover the regulatory "modes" that the cells adopt during heart organogenesis. The regulatory genes, however, can only specify the proteins that will be present.

Conclusions: To fully understand the timing and mechanisms underlying heart development, it is necessary to define the sequential synthesis, patterning, and interaction of the proteins, and of still other receptors, which eventually drive cells to organize into functioning organs.