title: Wnt/β-catenin signaling maintains the mesenchymal precursor pool for murine sinus horn formation.
abstract: BACKGROUND
  Canonical (β-catenin [Ctnnb1]-dependent) wingless-related MMTV integration site (Wnt) signaling plays an important role in the development of second heart field-derived structures of the heart by regulating precursor cell proliferation. The signaling pathways that regulate the most posterior elongation of the heart, that is, the addition of the systemic venous return from a Tbx18(+) precursor population, have remained elusive.
  
  
  OBJECTIVE
  To define the role of Ctnnb1-dependent Wnt signaling in the development of the cardiac venous pole.
  
  
  RESULTS
  We show by in situ hybridization analysis that Wnt pathway components are expressed and canonical Wnt signaling is active in the developing sinus horns. We analyzed sinus horn (Tbx18(cre))-specific Ctnnb1 loss- and gain-of-function mutant embryos. In Ctnnb1-deficient embryos, the dorsal part of the sinus horns is not myocardialized but consists of cells with at least partial fibroblast identity; the sinoatrial node is unaffected. Stabilization of Ctnnb1 in this domain results in the formation of undifferentiated cell aggregates. Analysis of cellular changes revealed a role of canonical Wnt signaling in proliferation of the Tbx18(+) mesenchymal progenitor cell population.
  
  
  CONCLUSIONS
  Wnt/β-catenin signaling maintains the Tbx18(+)Nkx2-5(-) mesenchymal precursor pool for murine sinus horn formation.
authors.affiliation: Institut für Molekularbiologie, OE5250, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Norden
authors.forename: Franziska
authors.initials: F
authors.lastname: Greulich
authors.forename: Carsten
authors.initials: C
authors.lastname: Rudat
authors.forename: Makoto Mark
authors.initials: MM
authors.lastname: Taketo
authors.forename: Andreas
authors.initials: A
authors.lastname: Kispert
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D055879:Gene Knock-In Techniques; D006321:Heart / Q000196:embryology* / Q000254:growth & development; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051153:Wnt Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D051176:beta Catenin / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics
chemical_list: C495267:CTNNB1 protein, mouse; D051153:Wnt Proteins; D051176:beta Catenin