Cardiac looping is a morphogenetic process that moves the developing chambers of the vertebrate heart into their approximate final positions. It involves the bending of the initially straight heart tube into an S-shaped loop; however, the mechanisms governing this process of S-looping have so far remained elusive. Now, Salim Abdelilah-Seyfried, Verónica Lombardo and colleagues reveal how S-looping morphogenesis is regulated in zebrafish embryos. They find that S-looping occurs simultaneously with the planar bending of the heart tube, a cardiac torsion and an anisotropic ballooning of the heart chambers, suggesting that these processes may, together, drive S-looping. They further show that Bmp signalling, a well-known regulator of organ morphogenesis, promotes S-looping. Bmp activity is stronger at the superior than at the inferior atrioventricular canal (AVC), generating an asymmetric pattern of Bmp signalling. This appears to promote myocardial cells to acquire conical and bottlenecked shapes, which in turn facilitates planar bending of the heart during S-looping. By knocking out cardiac TroponinT2a, a protein that promotes heart contraction, the authors also demonstrate that Bmp activity at the AVC is regulated by cardiac contractility. Thus, this study identifies key factors that shape heart morphology, which may eventually aid researchers in understanding the causes of human congenital heart defects.

• © 2019. Published by The Company of Biologists Ltd