title: Tbx18 function in epicardial development.
abstract: OBJECTIVE
  The embryonic epicardium is a source of smooth muscle cells and fibroblasts of the coronary vasculature and of the myocardium, but the molecular circuits that direct the temporal and spatial generation of these cell types from epicardium-derived cells are only partly known. We aimed to elucidate the functional significance of the conserved epicardial expression of the T-box transcription factor gene Tbx18 using transgenic technology in the mouse.
  
  
  RESULTS
  We show by cellular and molecular analyses that in Tbx18-deficient mice the epicardium is formed normally and that epicardial cells undergo an epithelial-mesenchymal transition, differentiate into smooth muscle cells and fibroblasts, and form a normal coronary vasculature and fibrous skeleton. Prolonged expression of Tbx18 in epicardium-derived cells by a transgenic approach in vivo does not affect the differentiation and migratory behaviour of these cells. In contrast, epicardial misexpression of a transcriptional activator version of Tbx18, Tbx18VP16, results in premature smooth muscle differentiation of epicardial cells. Inhibition of Notch and transforming growth factor beta receptor signalling in Tbx18VP16 expressing epicardial cells in explant cultures reverts this phenotype.
  
  
  CONCLUSIONS
  Tbx18 is dispensable for epicardial development, yet a repressive T-box function may be required to prevent premature smooth muscle cell differentiation by repressing transforming growth factor beta receptor and Notch signalling in the embryonic epicardium.
authors.affiliation: Institut für Molekularbiologie,  Medizinische Hochschule Hannover, OE5250, Carl-Neuberg-Str.1, Hannover D-30625,  Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Greulich
authors.forename: Henner F
authors.initials: HF
authors.lastname: Farin
authors.forename: Karin
authors.initials: K
authors.lastname: Schuster-Gossler
authors.forename: Andreas
authors.initials: A
authors.lastname: Kispert
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D003331:Coronary Vessels / Q000196:embryology / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D009131:Muscle, Smooth, Vascular / Q000196:embryology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010496:Pericardium / Q000196:embryology / Q000378:metabolism*; D010641:Phenotype; D051880:Receptors, Notch / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D046509:Tissue Culture Techniques; D015533:Transcriptional Activation
chemical_list: D051880:Receptors, Notch; D018125:Receptors, Transforming Growth Factor beta; D020825:T-Box Domain Proteins; C420983:Tbx18 protein, mouse