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.

Cardioids reveal self-organizing principles of human cardiogenesis

“…However, bilateral heart tubes and chambers can form in the absence of either endocardium (Ferdous et al, 2009) or foregut endoderm constriction (DeHaan and DeHaan, 1959;Li et al, 2004), but the mechanism is still unknown. This indicates the inherent capability of cardiac mesoderm to intrinsically form cavities and chambers in vivo (Ivanovitch et al, 2017), which is in agreement with the self-organization we observed in cardioids and chick embryo explants in vitro. Lateral plate mesoderm, a subtype closely related to cardiac mesoderm, has a similar potential to form a cavity -the pericardial body cavity (Schlueter and Mikawa, 2018).…”

“…We found that WNT and VEGF control CM and EC self-organization in cardioids. In vivo, cardiac ECs first form endocardial tubes, later become separated from the outer CM tube by an ECM-filled (cardiac jelly) interspace, and finally form the inner lining of the heart chambers (Abu- Issa and Kirby, 2007;Ivanovitch et al, 2017). How signaling coordinates these patterns and morphogenetic processes with specification was unclear.…”

Cell atlas of the foetal human heart and implications for autoimmune-mediated congenital heart block

“…EC6 uniquely expressed genes involved in fatty acid (FA) binding and transport including CD36 , FABP4 , and FABP5 , thereby providing the basis for the FA-biased energy metabolism that contributes up to 70% of cardiac ATP ( Supplementary material online , Figure S3 ). Unexpectedly, fast skeletal muscle troponin TNNT3 is specifically expressed in EC6 in the foetal heart, which was further confirmed by immunohistochemistry ( Figures 2 D–F and 3 A ). Furthermore, blood vessels formed by EC6 are characterized also by the presence of perivascular cells surrounding them.…”

“… 2 The cardiac progenitors arise from mesoderm and segregate into two populations that form first (FHF) and second (SHF) heart fields. 3 The FHF gives rise to the early cardiac tube that contributes to the left ventricle and parts of the atria whereas the SHF is placed within and at the entry of the developing tube and contributes to the outflow tract, right ventricle, and atria. 1 Genetic cell-fate-mapping studies in animal model systems have greatly enhanced the understanding of lineage contribution to diverse cell groups that constitute the heart.…”

Visualising the Cardiovascular System of Embryos of Biomedical Model Organisms with High Resolution Episcopic Microscopy (HREM)

“…Due to the central role the cardiovascular system plays in the embryonic, foetal and postnatal life, the genetic and biomechanical factors regulating normal cardiovascular development and the mechanisms underlying its pathologies are the focus of biomedical research [1,2,3,4,5,6,7]. For such research, a large number of tools for labelling active genes and gene products and for modifying or physically challenging their interplay during critical steps of development and growth were created and successfully established.…”