Tbx5a lineage tracing shows cardiomyocyte plasticity during zebrafish heart regeneration

During development, mesodermal progenitors from the first heart field (FHF) form a primitive cardiac tube, to which progenitors from the second heart field (SHF) are added. The contribution of FHF and SHF progenitors to the adult zebrafish heart has not been studied to date. Here we find, using genetic tbx5a lineage tracing tools, that the ventricular myocardium in the adult zebrafish is mainly derived from tbx5a+ cells, with a small contribution from tbx5a− SHF progenitors. Notably, ablation of ventricular tbx5a+-derived cardiomyocytes in the embryo is compensated by expansion of SHF-derived cells. In the adult, tbx5a expression is restricted to the trabeculae and excluded from the outer cortical layer. tbx5a-lineage tracing revealed that trabecular cardiomyocytes can switch their fate and differentiate into cortical myocardium during adult heart regeneration. We conclude that a high degree of cardiomyocyte cell fate plasticity contributes to efficient regeneration.Funding was through FPU12/03007 and BFU2014–56970–P (Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016, Programa Estatal de I+D+i Orientada a los Retos de la Sociedad Retos Investigación: Proyectos I+D+i 2016, del Ministerio de Economía competitividad e Industria), and co-funding by Fondo Europeo de Desarrollo Regional (FEDER) (H.S. and N.M.); Swiss National Science Foundation grant 31003A_159721, ANR-SNF collaborative Project 320030E-164245, and the ERC starting grant 337703–zebra–Heart (N.M.). A.E. is enrolled into PhD specialization Cutting Edge Microscopy offered by the Graduate School for Cellular and Biomedical Sciences (GCB) and the Microscopy Imaging Center (MIC). The CNIC is supported by the Ministry of Economy, Industry and Competitiveness (MEIC) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505). Further support was from the Canton of Zürich, project grant from the Swiss Heart Foundation (A.F. and C. Mosimann); the Swiss National Science Foundation (SNSF) professorship (PP00P3_139093) and a Marie Curie Career Integration Grant from the European Commission (CIG PCIG14-GA-2013-631984) (C. Mosimann).Peer reviewe