On the role of intrinsic and extrinsic forces in early cardiac S‐looping

Abstract

Background Looping is a crucial phase during heart development when the initially straight heart tube is transformed into a shape that more closely resembles the mature heart. Although the genetic and biochemical pathways of cardiac looping are well-studied, the biophysical mechanisms that actually effect the looping process remain poorly understood. Using a combined experimental (chick embryo) and computational (finite element modeling) approach, we study the forces driving early s-looping when the primitive ventricle moves to its definitive position inferior to the common atrium. Results New results from our study indicate that the primitive heart has no intrinsic ability to form an s-loop and that extrinsic forces are necessary to effect early s-looping. They support previous studies that established an important role for cervical flexure in causing early cardiac s-looping. Our results also show that forces applied by the splanchnopleure cannot be ignored during early s-looping and shed light on the role of cardiac jelly. Using available experimental data and computer modeling, we successfully developed and tested a hypothesis for the force mechanisms driving s-loop formation. Conclusions Forces external to the primitive heart tube are necessary in the later stages of cardiac looping. Experimental and model results support our proposed hypothesis for forces driving early s-looping.

How the embryonic chick brain twists

“…More recently, Shyer et al revealed the role of mechanical stresses in the formation of villi in the gut [8]. Forces extrinsic to the primitive heart tube also are important players during cardiac looping [14,26,40,41]. Results from these studies suggest that the SPL plays a mechanical role in facilitating cardiac torsion that may be similar to the role of the VM in inducing brain torsion reported here.…”

“…In a sense, this process can be considered as a transfer of chirality or L -R asymmetry, from the heart to the brain tube through mechanics. Following the first phase of cardiac looping (c-looping), brain torsion in turn ensures the normal helical looping of the heart during the subsequent s-looping [41]. This type of transfer of chirality between two co-developing organs at the same length scale has not previously been examined in detail, although the transfer of chirality from microscopic-to-macroscopic scale in plant tendrils has recently been studied [34].…”

Morphomechanics: transforming tubes into organs

“…The forces that drive s-looping apparently are exerted by external loads, including those supplied by the brain tube as it bends [31]. …”

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

“…It has been found, however, that this “ in vitro looping ” is simpler than the normal “ in situ looping ” since it produces heart loops that are bend only in a single plane (planar looping) but lack a helical shape (spatial looping) (Flynn et al, 1991; Latacha et al, 2005; Rémond et al, 2006; Ramasubramanian et al, 2013). Contemporary hypotheses of cardiac looping mechanics, therefore, attribute the bending of the tubular embryonic heart primarily to forces intrinsic to its myocardial wall (Latacha et al, 2005; Taber, 2006; Taber et al, 2010) while its deformation into helical shapes is attributed primarily to factors outside of the heart (Taber, 2006; Taber et al, 2010; Männer, 2013).…”