title: Tbx2 and Tbx3 induce atrioventricular myocardial development and endocardial cushion formation.
abstract: A key step in heart development is the coordinated development of the atrioventricular canal (AVC), the constriction between the atria and ventricles that electrically and physically separates the chambers, and the development of the atrioventricular valves that ensure unidirectional blood flow. Using knock-out and inducible overexpression mouse models, we provide evidence that the developmentally important T-box factors Tbx2 and Tbx3, in a functionally redundant manner, maintain the AVC myocardium phenotype during the process of chamber differentiation. Expression profiling and ChIP-sequencing analysis of Tbx3 revealed that it directly interacts with and represses chamber myocardial genes, and induces the atrioventricular pacemaker-like phenotype by activating relevant genes. Moreover, mutant mice lacking 3 or 4 functional alleles of Tbx2 and Tbx3 failed to form atrioventricular cushions, precursors of the valves and septa. Tbx2 and Tbx3 trigger development of the cushions through a regulatory feed-forward loop with Bmp2, thus providing a mechanism for the co-localization and coordination of these important processes in heart development.
authors: Institut für Molekularbiologie, Medizinische Hochschule Hannover, Germany.
authors: Reena
authors: R
authors: Singh
authors: Willem M
authors: WM
authors: Hoogaars
authors: Phil
authors: P
authors: Barnett
authors: Thomas
authors: T
authors: Grieskamp
authors: M Sameer
authors: MS
authors: Rana
authors: Henk
authors: H
authors: Buermans
authors: Henner F
authors: HF
authors: Farin
authors: Marianne
authors: M
authors: Petry
authors: Todd
authors: T
authors: Heallen
authors: James F
authors: JF
authors: Martin
authors: Antoon F M
authors: AF
authors: Moorman
authors: Peter A C
authors: PA
authors: 't Hoen
authors: Andreas
authors: A
authors: Kispert
authors: Vincent M
authors: VM
authors: Christoffels
mesh_terms: D000818:Animals; D001483:Base Sequence; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D054089:Endocardial Cushions / Q000196:embryology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; C491460:Tbx3 protein, mouse