Growth and Morphogenesis during Early Heart Development in Amniotes

Abstract

In this review, we will focus on the growth and morphogenesis of the developing heart, an aspect of cardiovascular development to which Antoon Moorman and colleagues have extensively contributed. Over the last decades, genetic studies and characterization of regionally regulated gene programs have provided abundant novel insights into heart development essential to understand the basis of congenital heart disease. Heart morphogenesis, however, is inherently a complex and dynamic three-dimensional process and we are far from understanding its cellular basis. Here, we discuss recent advances in studying heart morphogenesis and regionalization under the light of the pioneering work of Moorman and colleagues, which allowed the reinterpretation of regional gene expression patterns under a new morphogenetic framework. Two aspects of early heart formation will be discussed in particular: (1) the initial formation of the heart tube and (2) the formation of the cardiac chambers by the ballooning process. Finally, we emphasize that in addition to analyses based on fixed samples, new approaches including clonal analysis, single-cell sequencing, live-imaging and quantitative analysis of the data generated will likely lead to novel insights in understanding early heart tube regionalization and morphogenesis in the near future.

Keywords: cardiac crescent; cardiac differentiation; cardiomyocyte; first heart field; heart tube; live-imaging; second heart field.

Figure 1

3-dimensional analysis of heart tube formation. (A–C) show optical sections of 3D reconstructions obtained by light-sheet microscopy from E7.5 (A); E8 (B) and E8.25 (C) embryos. Rosa26GFP; Mesp1^cre/+; R26Rtdtomato embryos are shown in (A,B); while a Mesp1^cre/+; R26RmT/mG embryo is shown in (C); Ectoderm and endoderm are shown in green and mesoderm in yellow (A,B) or red (C); (D,E) show simultaneous display of the 3D reconstructions of the foregut pocket (blue), cardiac crescent (red) and whole embryo (green) from E7.5 (D) and E8 (E) embryos; (F–G’) show magnified 3D views of the cardiac region of the embryo 3D models in (D,E); The whole-embryo volume (green) has been transparented for appreciation of the details of the cardiac region. (F,G) show ventro-lateral views and (F’,G’) show dorso-lateral views; (H,H’) a reconstruction of the linear heart tube from an E8.3 embryo; (H) shows a dorsal view and (H’) a lateral view. The image indicates the structures derived at this stage from the FHF: left ventricle and part of the atria and SHF: right ventricle and part of the atria. ht, heart tube; cc, cardiac crescent; fg, foregut pocket; end, endoderm; mes, mesoderm; ect, ectoderm; emb, embryo; ap, arterial pole; vp, venous poles; lv, left ventricle primordium; rv, right ventricle primordium; la, left atrium primordium; ra, right atrium primordium.

Figure 2

The ballooning Model for Cardiac Chamber Initiation. Schemes show ventral (A) and lateral–partially open–(B) views of the looping amniote heart. The schemes are inspired in previous Figures published by Anton Moorman and colleagues [55]. Note how chambers develop at localized areas of the outer curvature of the heart tube and not form cylindrical segments of the heart tube. OFT, outflow tract, RV, right ventricle, LV, left ventricle, RA, right atrium, LA, left atrium, IFT, inflow tract, AVC, atrio-ventricular canal.