title: Heart chamber size in zebrafish is regulated redundantly by duplicated tbx2 genes.
abstract: The Tbx2 transcription factor is implicated in growth control based on its association with human cancers. In the heart, Tbx2 represses cardiac differentiation to mediate development of the atrioventricular canal (AVC). The zebrafish genome retains two tbx2 genes, and both are required for formation of the AVC. Here, we show that both genes are also expressed earlier in the primitive heart tube, and we describe a previously unrecognized role for Tbx2 in promoting proliferation of presumptive myocardium at the heart tube stage. In contrast to single knockdowns, depletion of both gene products causes chamber defects, resulting in an expanded atrium and a smaller ventricle, associated with decreased proliferation of ventricular cardiomyocytes. The phenotype correlates with changes in the expression for known cardiac growth factors. Therefore, in zebrafish, two tbx2 genes are functionally redundant for regulating chamber development, while each gene is required independently for development of the AVC.
authors: Department of Surgery, Weill Cornell Medical College, New York, New York 10065, USA.
authors: Anya
authors: A
authors: Sedletcaia
authors: Todd
authors: T
authors: Evans
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D049109:Cell Proliferation; D004625:Embryo, Nonmammalian; D018628:Gene Dosage / Q000502:physiology; D020440:Gene Duplication / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology* / Q000254:growth & development; D006330:Heart Defects, Congenital / Q000196:embryology / Q000235:genetics / Q000662:veterinary; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology; D009929:Organ Size / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics* / Q000254:growth & development; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
chemical_list: D020825:T-Box Domain Proteins; D029961:Zebrafish Proteins; C491461:tbx2a protein, zebrafish