BMP signaling controls zebrafish cardiac looping morphogenesis.

VERÓNICA A. LOMBARDO; SALIM ABDELILAH-SEYFRIED; MELINA HEISE; MOTAHAREH MOGHTADAEI

Rosario

Jornada; Jornada Cientifica del Instituto de Biologia Molecular y Celular de Rosario; 2019

IBR-CONICET-UNR

Cardiac looping is a morphogenetic process during vertebrate heart development which brings the developing heart chambers into an approximation of their definitive topographical relationships. Abnormalities in this process result in human congenital heart defects. We analyze cardiac looping morphogenesis in the zebrafish embryo and identify three distinct cell- and tissue-scale transformations: i) myocardial cells shape change from cuboidal to conical at the superior atrioventricular region contributes to S-shaped bending; ii) torsional deformation close to the outflow tract brings to a torque-like winding of the entire heart tube between its two poles; iii) anisotropic growth of cardiomyocytes causes ballooning of the ventricle and atrium along their outer curvatures which reinforces S-shaping of the heart. During cardiac looping, Bone morphogenetic protein (Bmp) pathway signaling has a regional patterning which correlates with bending of the nascent heart tube. Upon its pharmacological or genetic inhibition, myocardial cells maintain cuboidal cell shapes and S-shaped bending is impaired. These results provide novel insights into the molecular control of cardiac looping morphogenesis in the zebrafish with relevance for a more comprehensive understanding of human congenital heart defects.