title: Lack of Genetic Interaction between Tbx18 and Tbx2/Tbx20 in Mouse Epicardial Development.
abstract: The epicardium, the outermost layer of the heart, is an essential source of cells and signals for the formation of the cardiac fibrous skeleton and the coronary vasculature, and for the maturation of the myocardium during embryonic development. The molecular factors that control epicardial mobilization and differentiation, and direct the epicardial-myocardial cross-talk are, however, insufficiently understood. The T-box transcription factor gene Tbx18 is specifically expressed in the epicardium of vertebrate embryos. Loss of Tbx18 is dispensable for epicardial development, but may influence coronary vessel maturation. In contrast, over-expression of an activator version of TBX18 severely impairs epicardial development by premature differentiation of epicardial cells into SMCs indicating a potential redundancy of Tbx18 with other repressors of the T-box gene family. Here, we show that Tbx2 and Tbx20 are co-expressed with Tbx18 at different stages of epicardial development. Using a conditional gene targeting approach we find that neither the epicardial loss of Tbx2 nor the combined loss of Tbx2 and Tbx18 affects epicardial development. Similarly, we observed that the heterozygous loss of Tbx20 with and without additional loss of Tbx18 does not impact on epicardial integrity and mobilization in mouse embryos. Thus, Tbx18 does not function redundantly with Tbx2 or Tbx20 in epicardial development.
authors.affiliation: Institut für Molekularbiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Greulich
authors.affiliation: Institut für Molekularbiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Rudat
authors.affiliation: Institut für Molekularbiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Henner F
authors.initials: HF
authors.lastname: Farin
authors.affiliation: Department of Anatomy, Embryology and Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Christoffels
authors.affiliation: Institut für Molekularbiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kispert
mesh_terms: D000483:Alleles; D000818:Animals; D004843:Epistasis, Genetic; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D010496:Pericardium / Q000196:embryology* / Q000378:metabolism*; D010641:Phenotype; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; C420983:Tbx18 protein, mouse; C486013:Tbx20 protein, mouse