Alexandre Francou and colleagues have investigated cell shape in an epithelial sheet of cardiac progenitor cells, known as the second heart field, that make a late contribution to the mouse heart during embryonic development. Perturbation of second heart field deployment to the arterial and venous poles of the growing heart tube results in a spectrum of congenital heart defects. Francou et al visualised the apical membrane of cells throughout the epithelium by staining for filamentous actin. Data segmentation and image analysis revealed that cells in the posterior region of the epithelium have a larger apical surface and are more elongated than cells in the anterior region, and are elongated in a direction towards the arterial pole of the heart. Wound assay experiments indicate that cell stretching results from tissue-wide forces leading to oriented epithelial stress and polarised accumulation of junctional actomyosin. Time course and mutant embryo analyses suggest that addition of progenitor cells to the heart is a source of tension in the epithelium. Furthermore, cell division in the plane of the epithelium and the growth of cell clusters are oriented in the same direction as cell elongation, suggesting that oriented tension in turn contributes to cell deployment to the cardiac poles through biomechanical feedback. Nuclear accumulation of YAP/TAZ, an activator of proliferation in response to mechanical stress, is observed in the posterior region of the epithelium and embryo culture in the presence of a YAP inhibitor decreases proliferation and leads to defective arterial pole development. Together these findings identify epithelial tension as a driver of second heart field deployment in a new biomechanical model for heart tube elongation. Further dissection of the tension-driven motor promoting heart tube extension may lead to the identification of novel pathways involved in congenital heart defects.

Francou et al., 2017, Epithelial tension in the second heart field promotes mouse heart tube elongation. Nature Communications 8:14770.

 

Contact: Robert.Kelly@univ-amu.fr