title: Tbx20 Is an Essential Regulator of Embryonic Heart Growth in Zebrafish.
abstract: The molecular mechanisms that regulate cardiomyocyte proliferation during embryonic heart growth are not completely deciphered yet. In a forward genetic N-ethyl-N-nitrosourea (ENU) mutagenesis screen, we identified the recessive embryonic-lethal zebrafish mutant line weiches herz (whz). Homozygous mutant whz embryos display impaired heart growth due to diminished embryonic cardiomyocyte proliferation resulting in cardiac hypoplasia and weak cardiac contraction. By positional cloning, we found in whz mutant zebrafish a missense mutation within the T-box 20 (Tbx20) transcription factor gene leading to destabilization of Tbx20 protein. Morpholino-mediated knock-down of Tbx20 in wild-type zebrafish embryos phenocopies whz, indicating that the whz phenotype is due to loss of Tbx20 function, thereby leading to significantly reduced cardiomyocyte numbers by impaired proliferation of heart muscle cells. Ectopic overexpression of wild-type Tbx20 in whz mutant embryos restored cardiomyocyte proliferation and heart growth. Interestingly, ectopic overexpression of Tbx20 in wild-type zebrafish embryos resulted, similar to the situation in the embryonic mouse heart, in significantly reduced proliferation rates of ventricular cardiomyocytes, suggesting that Tbx20 activity needs to be tightly fine-tuned to guarantee regular cardiomyocyte proliferation and embryonic heart growth in vivo.
authors.affiliation: Molecular Cardiology, Department of Medicine II, University of Ulm, Ulm, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Just
authors.affiliation: Department of Medicine II, University of Ulm, Ulm, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Raphel
authors.affiliation: Molecular Cardiology, Department of Medicine II, University of Ulm, Ulm, Germany.
authors.forename: Ina M
authors.initials: IM
authors.lastname: Berger
authors.affiliation: Molecular Cardiology, Department of Medicine II, University of Ulm, Ulm, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Bühler
authors.affiliation: Department of Medicine II, University of Ulm, Ulm, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Keßler
authors.affiliation: Molecular Cardiology, Department of Medicine II, University of Ulm, Ulm, Germany.|Department of Medicine II, University of Ulm, Ulm, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Rottbauer
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D000066630:Ectopic Gene Expression; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006321:Heart / Q000196:embryology*; D009154:Mutation; D032383:Myocytes, Cardiac / Q000378:metabolism; D038081:Organogenesis / Q000235:genetics*; D010641:Phenotype; D020825:T-Box Domain Proteins / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: D020825:T-Box Domain Proteins; D029961:Zebrafish Proteins; C486014:tbx20 protein, zebrafish