A new hypothesis for foregut and heart tube formation based on differential growth and actomyosin contraction

Abstract

For decades, it was commonly thought that the bilateral heart fields in the early embryo fold directly towards the midline, where they meet and fuse to create the primitive heart tube. Recent studies have challenged this view, however, suggesting that the heart fields fold diagonally. As early foregut and heart tube morphogenesis are intimately related, this finding also raises questions concerning the traditional view of foregut formation. Here, we combine experiments on chick embryos with computational modeling to explore a new hypothesis for the physical mechanisms of heart tube and foregut formation. According to our hypothesis, differential anisotropic growth between mesoderm and endoderm drives diagonal folding. Then, active contraction along the anterior intestinal portal generates tension to elongate the foregut and heart tube. We test this hypothesis using biochemical perturbations of cell proliferation and contractility, as well as computational modeling based on nonlinear elasticity theory including growth and contraction. The present results generally support the view that differential growth and actomyosin contraction drive formation of the foregut and heart tube in the early chick embryo.

The heart tube forms and elongates through dynamic cell rearrangement coordinated with foregut extension

“…In addition to cell rearrangement, hypertrophy and differential proliferation likely shape the early heart tube (Hosseini et al, 2017;Shi et al, 2014). In our confocal imaging, heart cells seemed to enlarge during heart tube formation (Fig.…”

“…2B′,arrow; note that the cell streams, which are initially aligned mediolaterally, are now oriented diagonally along the anteroposterior axis). This diagonal folding is thought to be important for realigning the initial mediolateral polarity of the bilateral heart fields to the anterior-posterior direction (Abu-Issa and Kirby, 2008;Hosseini et al, 2017). The coordinated movements between the heart primordia and AIP suggest that diagonal folding of the heart primordia may be driven by medial convergence and posteriorward motion of the AIP (Fig.…”

“…One may wonder whether compromised heart extension after Y27632 exposure was indirectly caused via AIP defects, as actomyosin contraction along the AIP was suggested to support heart lengthening (Hosseini et al, 2017). Although the AIP stopped converging and relaxed immediately after Y27632 exposure, it resumed converging/descending within 2 h (Movie 6).…”

“…Recent studies have suggested that the endoderm plays an active mechanical role in fusion of the paired heart primordia, pulling them toward the midline where they appose and fuse (Aleksandrova et al, 2015;Varner and Taber, 2012;Ye et al, 2015). In addition, a recent model proposes that endodermal myosin contraction around the AIP generates posteriorward forces that assist the elongation of the foregut and heart tube (Hosseini et al, 2017), but the extent to which movements of these two tissues are coordinated is unknown.…”

Embryonic organoids recapitulate early heart organogenesis

“…Heart organogenesis requires cardiac progenitors to interact with surrounding tissues through mechanical interactions and the secretion of cardiac-inducing factors (Miquerol and Kelly, 2013). These involved tissues especially include the endothelium (Brutsaert, 2003;Brutsaert et al, 1998;Narmoneva et al, 2004) and foregut (Hosseini et al, 2017;Kidokoro et al, 2018;Lough and Sugi, 2000;Nascone and Mercola, 1995;Schultheiss et al, 1995;Varner and Taber, 2012).…”