Wnt/β-catenin signaling maintains the mesenchymal precursor pool for murine sinus horn formation

Julia Norden, Franziska Greulich, Carsten Rudat, Makoto Mark Taketo, Andreas Kispert

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

RATIONALE: 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. METHODS AND 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)-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 Tbx18Nkx2-5 mesenchymal precursor pool for murine sinus horn formation.

Original languageEnglish
Pages (from-to)e42-e50
JournalCirculation Research
Volume109
Issue number6
DOIs
StatePublished - 2 Sep 2011
Externally publishedYes

Keywords

  • β-catenin
  • canonical Wnt signaling
  • cardiac progenitor
  • sinus horn

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