The role of mechanical forces in dextral rotation during cardiac looping in the chick embryo

Abstract

Cardiac looping is a vital morphogenetic process that transforms the initially straight heart tube into a curved tube normally directed toward the right side of the embryo. While recent work has brought major advances in our understanding of the genetic and molecular pathways involved in looping, the biophysical mechanisms that drive this process have remained poorly understood. This paper examines the role of biomechanical forces in cardiac rotation during the initial stages of looping, when the heart bends and rotates into a c-shaped tube (c-looping). Embryonic chick hearts were subjected to mechanical and chemical perturbations, and tissue stress and strain were studied using dissection and fluorescent labeling, respectively. The results suggest that (1) the heart contains little or no intrinsic ability to rotate, as external forces exerted by the splanchnopleure (SPL) and the omphalomesenteric veins (OVs) drive rotation; (2) unbalanced forces in the omphalomesenteric veins play a role in left-right looping directionality; and (3) in addition to ventral bending and rightward rotation, the heart tube also bends slightly toward the right. The results of this study may help investigators searching for the link between gene expression and the mechanical processes that drive looping.

Morphogenetic adaptation of the looping embryonic heart to altered mechanical loads

“…Statistical significance was confirmed by 2 test (P Ͻ 0.025). These results support previous notions that the OVs play a key role in establishing left-right directionality, with both OVs tending to push the heart to the opposite side (Voronov et al, 2004). In addition, we speculate that asymmetric contraction of the conotruncus ensures rightward looping when both veins are absent.…”

“…During c-looping, the heart tube undergoes ventral bending and dextral torsion to create a cshaped tube, with the outer (convex) curvature normally directed toward the right side of the embryo (Mä nner, 2000). Previous work has shown that bending is driven primarily by morphogenetic forces that arise within the heart tube (Butler, 1952;Manning and McLachlan, 1990;Latacha et al, 2005), but torsion is caused by loads exerted on the heart by neighboring tissues (Voronov et al, 2004). The present study illustrates the inadequacy of this dichotomous perspective, revealing a causal relationship between forces acting on the heart and those developed within the heart.…”

“…6B). It is important to note that Itasaki et al (1991) originally suggested this mechanism for torsion during early c-looping, but later experiments showed the OVs and SPL are primarily responsible for early torsion (Voronov et al, 2004). Here, we suggest that such a mechanism may in fact occur, but only if normal SPL loading is perturbed.…”

“…1, 2A). All of these constraints apply mechanical loads that likely influence looping morphology (Manasek, 1983;Voronov and Taber, 2002;Voronov et al, 2004;Ramasubramanian et al, 2005).…”

“…Moreover, when the SPL was removed from partially looped stage 11 hearts, the hearts untwisted within minutes and resumed normal torsion up to 12 hr later. This behavior was unexpected, as Voronov and colleagues have shown that the SPL plays an important role in the torsional component of c-looping (Voronov and Taber, 2002;Voronov et al, 2004). These authors, however, followed looping for only 6 hr after SPL removal at stage 10.…”