title: Tbx20 is essential for cardiac chamber differentiation and repression of Tbx2.
abstract: Tbx20, a member of the T-box family of transcriptional regulators, shows evolutionary conserved expression in the developing heart. In the mouse, Tbx20 is expressed in the cardiac crescent, then in the endocardium and myocardium of the linear and looped heart tube before it is restricted to the atrioventricular canal and outflow tract in the multi-chambered heart. Here, we show that Tbx20 is required for progression from the linear heart tube to a multi-chambered heart. Mice carrying a targeted mutation of Tbx20 show early embryonic lethality due to hemodynamic failure. A linear heart tube with normal anteroposterior patterning is established in the mutant. The tube does not elongate, indicating a defect in recruitment of mesenchyme from the secondary heart field, even though markers of the secondary heart field are not affected. Furthermore, dorsoventral patterning of the tube, formation of working myocardium, looping, and further differentiation and morphogenesis fail. Instead, Tbx2, Bmp2 and vinexin alpha (Sh3d4), genes normally restricted to regions of primary myocardium and lining endocardium, are ectopically expressed in the linear heart tube of Tbx20 mutant embryos. Because Tbx2 is both necessary and sufficient to repress chamber differentiation (Christoffels et al., 2004a; Harrelson et al., 2004), Tbx20 may ensure progression to a multi-chambered heart by repressing Tbx2 in the myocardial precursor cells of the linear heart tube destined to form the chambers.
authors.affiliation: Institut für Molekularbiologie, Medizinische Hochschule Hannover, 30625 Hannover, Germany.
authors.forename: Manvendra K
authors.initials: MK
authors.lastname: Singh
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Christoffels
authors.forename: José M
authors.initials: JM
authors.lastname: Dias
authors.forename: Mark-Oliver
authors.initials: MO
authors.lastname: Trowe
authors.forename: Marianne
authors.initials: M
authors.lastname: Petry
authors.forename: Karin
authors.initials: K
authors.lastname: Schuster-Gossler
authors.forename: Antje
authors.initials: A
authors.lastname: Bürger
authors.forename: Johan
authors.initials: J
authors.lastname: Ericson
authors.forename: Andreas
authors.initials: A
authors.lastname: Kispert
mesh_terms: D000818:Animals; D017209:Apoptosis; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000033:anatomy & histology* / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D012097:Repressor Proteins; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; C486013:Tbx20 protein, mouse