Using the zebrafish as an in vivo model for development, this study shows that sustained Wt1 ortholog expression in cardiomyocytes impaired their maturation including sarcomere assembly, ultimately affecting cardiac morphology and function. Indeed, a subset of wt1a- or wt1b-expressing cardiomyocytes changed their cell adhesion properties, delaminated from the myocardial epithelium and assumed an epicardium-like phenotype. From this study, it was concluded that Wt1 plays a yet undescribed role for cardiomyocyte differentiation by repressing chromatin opening at specific genomic loci and that sustained ectopic expression of wt1a or wt1b in cardiomyocytes can lead to their transformation into epicardial cells.
Video: Time lapse recording of wt1b overexpressing heart in zebrafish embryos between 5 and 6 days post-fertilization (dpf). Note how the extruded cells flatten down during the time course of the movie (Yellow arrow). Elapsed time since initial acquisition is stamped in each panel. Shown is a ventral view with the head to the top.
I. J. Marques, A. Ernst, P. Arora, A. Vianin, T. Hetke, A. Sanz-Morejón, U. Naumann, A. Odriozola ,X. Langa, L. Andrés-Delgado, B. Zuber, C. Torroja, M. Osterwalder, F. C. Simões, C. Englert & N. Mercader:
Wt1 transcription factor impairs cardiomyocyte specification and drives a phenotypic switch from myocardium to epicardium
Development (2022) 149 (6): dev200375.
