title: Ventricular cell fate can be specified until the onset of myocardial differentiation.
abstract: The mechanisms that govern specification of various cell types that constitute vertebrate heart are not fully understood. Whilst most studies of heart development have utilised the mouse embryo, we have used an alternative model, embryos of the frog Xenopus laevis, which permits direct experimental manipulation of a non-essential heart. We show that in this model pluripotent animal cap explants injected with cardiogenic factor GATA4 mRNA express pan-myocardial as well as ventricular and proepicardial markers. We found that cardiac cell fate diversification, as assessed by ventricular and proepicardial markers, critically depends on tissue integrity, as it is disrupted by dissociation but can be fully restored by inhibition of the BMP pathway and partially by Dkk-1. Ventricular and proepicardial cell fates can also be restored in reaggregated GATA4-expressing cells upon transplantation into a host embryo. The competence of the host embryo to induce ventricular and proepicardial markers gradually decreases with the age of the transplant and is lost by the onset of myocardial differentiation at the late tailbud stage (st. 28). The influence of the host on the transplant was not limited to diversification of cardiac cell fates, but also included induction of growth and rhythmic beating, resulting in generation of a secondary heart-like structure. Our results additionally show that efficient generation of secondary heart requires normal axial patterning of the host embryo. Furthermore, secondary hearts can be induced in a wide range of locations within the host, arguing that the host embryo provides a permissive environment for development of cardiac patterning, growth and physiological maturation. Our results have implications for a major goal of cardiac regenerative medicine, differentiation of ventricular myocardium.
authors.affiliation: School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, Wales, UK.
authors.forename: Simona
authors.initials: S
authors.lastname: Caporilli
authors.affiliation: School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3AX, Wales, UK. Electronic address: latinkicb@cardiff.ac.uk.
authors.forename: Branko V
authors.initials: BV
authors.lastname: Latinkic
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004625:Embryo, Nonmammalian / Q000166:cytology; D050991:GATA4 Transcription Factor / Q000502:physiology; D006352:Heart Ventricles / Q000166:cytology / Q000196:embryology*; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000502:physiology*; D046509:Tissue Culture Techniques; D029867:Xenopus Proteins / Q000502:physiology; D014982:Xenopus laevis
chemical_list: D050991:GATA4 Transcription Factor; C494751:GATA4 protein, Xenopus; D029867:Xenopus Proteins