Heart fields and cardiac morphogenesis

Abstract

In this review, we focus on two important steps in the formation of the embryonic heart: (i) the progressive addition of late differentiating progenitor cells from the second heart field that drives heart tube extension during looping morphogenesis, and (ii) the emergence of patterned proliferation within the embryonic myocardium that generates distinct cardiac chambers. During the transition between these steps, the major site of proliferation switches from progenitor cells outside the early heart to proliferation within the embryonic myocardium. The second heart field and ballooning morphogenesis concepts have major repercussions on our understanding of human heart development and disease. In particular, they provide a framework to dissect the origin of congenital heart defects and the regulation of myocardial proliferation and differentiation of relevance for cardiac repair.

Figure 1.

Early events in heart tube formation. (A) The forming human heart in a ventral view and transverse section at stage 9 showing the heart tube open dorsally to foregut endoderm. (B) Quantitative 3D reconstruction of Ki67-positive cells at stage 10 showing the paucity of proliferating cells in the myocardium compared with the dorsal pericardial wall. Note the local increase in proliferation (arrowheads) representing the initiation of ballooning morphogenesis. (From Sizarov et al. 2011; reproduced, with permission.)

Figure 2.

The contribution of the second heart field to heart tube extension. Cartoon showing the progressive addition of second heart field progenitor cells (dark blue) to the elongating heart tube between 7.5 and 9.5 d of mouse development. In the midgestation heart (right), second heart field–derived parts of the heart are indicated in blue. (From Kelly 2012; reproduced, with permission.)

Figure 3.

The emergence of patterned proliferation in the embryonic heart. (A) Reconstructions of the myocardium and lumen of a mouse heart at day 11 of development in ventral views showing elevated BrdU incorporation in forming camber myocardium at the outer curvature of the heart tube. (B) Patterned proliferation in the heart is regulated by transcription factors including T-box family members and NKX2-5 (right). (Panel A reproduced, with permission, from de Boer et al. 2012.)