Morphogenetic control of zebrafish cardiac looping by Bmp signaling

Abstract

Cardiac looping is an essential and highly conserved morphogenetic process that places the different regions of the developing vertebrate heart tube into proximity of their final topographical positions. High-resolution 4D live imaging of mosaically-labelled cardiomyocytes reveals distinct cardiomyocyte behaviors that contribute to the deformation of the entire heart tube. Cardiomyocytes acquire conical cell shapes, which is most pronounced at the superior wall of the atrioventricular canal and contributes to S-shaped bending. Torsional deformation close to the outflow tract contributes to a torque-like winding of the entire heart tube between its two poles. Anisotropic growth of cardiomyocytes based on their positions reinforces S-shaping of the heart. During cardiac looping, Bone morphogenetic protein pathway signaling is strongest at the future superior wall of the atrioventricular canal. Upon pharmacological or genetic inhibition of Bone morphogenetic protein signalling, myocardial cells at the superior wall of the atrioventricular canal maintain cuboidal cell shapes and S-shaped bending is impaired. This inventory of cellular rearrangements and cardiac looping regulation may also be relevant for understanding the etiology of human congenital heart defects.

Twisting of the heart tube during cardiac looping is atbx5-dependent and tissue-intrinsic process

“…The clockwise rotation we observed in the ventricle is in the same direction as the rotation that was observed during linear heart tube formation (38). Recently, a clockwise rotation was also described in the OFT of the zebrafish heart at later cardiac looping stages (40-54 hpf) (49). Together, these observations suggest that a clockwise rotation of the cardiac tissue is initiated during linear heart tube formation (20-26 hpf) and that this clockwise rotation continues in the ventricle (28-42 hfp) during looping initiation and continues in the OFT (40-54 hpf) during the late looping stage.…”

“…Epithelial remodeling is an important driver for asymmetric rotation of the Drosophila gut tube or looping of the chick midgut and heart tube (19, 28, 47). In the zebrafish heart tube epithelial remodeling, as observed by changes in cardiomyocyte shape and cell boundaries, occurs during looping morphogenesis as well (27, 48, 49). Hence, we next proceeded by assessing the shape of ventricular cardiomyocytes between 30 hpf and 42 hpf (Fig.…”

“…Like the Drosophila gut tube, the heart tube consists of an epithelial tissue with distinct apical-basal polarity (for references see (16)). During heart looping and chamber ballooning, the epithelium undergoes remodeling, which coincides with regional cell shape changes (27, 48, 49). Interestingly, defective chamber expansion is accompanied in oug embryos by failure of the cells at the outer curvature of the ventricle to remodel anisotropically, a process that is regulated by non-canonical Wnt- and PCP-signaling (27).…”

Automatic segmentation and cardiac mechanics analysis of evolving zebrafish using deep-learning

“…Similarly, a pattern was observed within the volumetric change of the atrium, albeit in an inverse manner. (Figure 6A-D) increase between 2 dpf to 3 dpf where morphology changed by cardiac looping [24] ( Figure 6E-F). Also, the active trabeculation process [16; 23] which increases contractility of ventricle affects ESV of ventricle at 5 dpf from 4 dpf.…”

From Stripes to a Beating Heart: Early Cardiac Development in Zebrafish

“…Active Bmp signaling drives general differentiation of cardiomyocytes, while chemical perturbation of Bmp signaling at 24 to 48 hpf leads to an increase in BA size at the expense of arterial pole myocardium, suggesting that Bmp patterns the zebrafish SHF by defining myocardial versus smooth muscle fates [92,100]. Asymmetric Nodal signaling on the left and Bmp signaling act in parallel to establish zebrafish cardiac laterality and correct heart looping [23,115,116]. From 48 hpf onwards, endocardial Notch signaling has been implicated in triggering bmp2b and bmp4 expression that prompts pericardium progenitor cluster formation, and zebrafish lacking the Bmp receptor Acvr1l fail to form a proepicardium [70,117].…”