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

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 have been 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. Developmental Dynamics 242:801–816, 2013. © 2013 Wiley Periodicals, Inc.