Cardiac looping may be driven by compressive loads resulting from unequal growth of the heart and pericardial cavity. Observations on a physical simulation model

Abstract

The transformation of the straight embryonic heart tube into a helically wound loop is named cardiac looping. Such looping is regarded as an essential process in cardiac morphogenesis since it brings the building blocks of the developing heart into an approximation of their definitive topographical relationships. During the past two decades, a large number of genes have been identified which play important roles in cardiac looping. However, how genetic information is physically translated into the dynamic form changes of the looping heart is still poorly understood. The oldest hypothesis of cardiac looping mechanics attributes the form changes of the heart loop (ventral bending → simple helical coiling → complex helical coiling) to compressive loads resulting from growth differences between the heart and the pericardial cavity. In the present study, we have tested the physical plausibility of this hypothesis, which we call the growth-induced buckling hypothesis, for the first time. Using a physical simulation model, we show that growth-induced buckling of a straight elastic rod within the confined space of a hemispherical cavity can generate the same sequence of form changes as observed in the looping embryonic heart. Our simulation experiments have furthermore shown that, under bilaterally symmetric conditions, growth-induced buckling generates left- and right-handed helices (D-/L-loops) in a 1:1 ratio, while even subtle left- or rightward displacements of the caudal end of the elastic rod at the pre-buckling state are sufficient to direct the buckling process toward the generation of only D- or L-loops, respectively. Our data are discussed with respect to observations made in biological “models.” We conclude that compressive loads resulting from unequal growth of the heart and pericardial cavity play important roles in cardiac looping. Asymmetric positioning of the venous heart pole may direct these forces toward a biased generation of D- or L-loops.

Bending and twisting the embryonic heart: a computational model for c-looping based on realistic geometry

“…This mechanism for bending extends the original idea of Patten (1922) that the HT buckles as it grows longer within a confined space, but the authors acknowledge that this idea seems inconsistent with bending of isolated hearts (Bayraktar and Männer, 2014). These authors also show that looping direction can be determined by a small initial offset in the lateral position of the caudal end of the HT.…”

Development of the human heart

“…Looping is an elusive process during which the dorsal mesocardium ruptures along its midline and the heart tube bends to the right, acquiring a C shape. With ongoing development, the bending of the heart tube becomes more complex, acquiring an S‐shape (Bayraktar & Manner, ; Manner, ).…”

“…Looping is an elusive process during which the dorsal mesocardium ruptures along its midline and the heart tube bends to the right, acquiring a C shape. With ongoing development, the bending of the heart tube becomes more complex, acquiring an S-shape (Bayraktar & Manner, 2014;Manner, 2009). While looping, the heart tube increases five-fold in length due to the continuous addition of newly differentiated cardiomyocytes, rather than by proliferation of the cardiomyocytes of the heart tube (de Boer, van den Berg, de Boer, Moorman, & Ruijter, 2012a;Soufan et al, 2006).…”

Left–Right Patterning: Breaking Symmetry to Asymmetric Morphogenesis

“…Placing a silicone rod under various compressive loads within a confined space, which models cardiac growth within the pericardial cavity, can generate the same changes of form as occurs in the looping embryonic heart [42]. Providing the model with no L-R bias results in a 50:50 split between D- and levo (L)-loops, whereas inputting only very subtle L-R asymmetric displacements of the caudal end (as occurs in embryos) results in consistently lateralized loops [42]. Thus, differential growth of the linear cardiac tube and the pericardial cavity resulting in compressive loads being placed on the heart can drive a buckling process which results in morphological changes in the tube that closely mimic looping.…”