Review
Signals from both sides: Control of cardiac development by the endocardium and epicardium

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Abstract

It is readily apparent that the process of heart development is an intricate one, in which cells derived from many embryonic sources coalesce and coordinate their behaviors and development, resulting in the mature heart. The behaviors and mechanisms of this process are complex, and still incompletely understood. However, it is readily apparent that communication between diverse cell types must be involved in this process. The signaling that emanates from epicardial and endocardial sources is the focus of this review.

Section snippets

Epicardial and endocardial signaling during cardiac development

Exquisite control and regulation is required for development of a properly functioning heart. As the heart progresses from mesoderm to a simple tube to a complex four-chambered structure, each step along this progression requires precise regulation of cellular behavior by a variety of sources. The hypoblast [1], [2], epiblast [3], endoderm [4], neural tissue [5], [6], [7], [8], endocardium [9], [10], [11], [12], [13], and epicardium [9], [10], [14] all signal to developing/mature muscle or

Embryonic origins of the endocardium, epicardium, and myocardium

While a thorough discussion of the early embryonic development of the components of the mature heart is not within the scope of this review, a brief review of the embryonic origins and mechanisms that give rise to these tissues is useful for this discussion. Numerous excellent and more exhaustive reviews of endocardial [20], [21], [22], [23], [24], epicardial [25], [26], [27], [28], [29], and myocardial [30], [31], [32] development and origins are available. To summarize, endocardial and

Signals from the endocardium

The endocardium secretes signals that act upon other components of the developing heart in a paracrine manner, as well as factors that act upon the endocardium itself in an autocrine fashion. The endocardium also receives and responds to cues from other tissue sources during heart development, such as VEGF signaling from the myocardium that represses delamination of cells of the endocardial epithelium prior to endocardial cushion formation [17]. These interactions lie outside the scope of this

Signals from the epicardium

The proepicardium, epicardium, and epicardially derived cells are critical for normal heart development. These structures not only provide a major portion of the cells that comprise the coronary vasculature, the epicardium also plays an important role in modulating the development of the myocardium. Naturally, as diseases related to the coronary vasculature are a major cause of death, interest in understanding the normal development of the transient and definitive structures of this tissue has

Acknowledgements

The authors would like to thank members of our laboratory for helpful comments and discussion. DMB is supported by NIH HL37675 and NIH HL079050. TKS is supported by AHA 0415252B and NIH HL079050.

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