title: Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes.
abstract: Osteoblasts and chondrocytes are involved in building up the vertebrate skeleton and are thought to differentiate from a common mesenchymal precursor, the osteo-chondroprogenitor. Although numerous transcription factors involved in chondrocyte and osteoblast differentiation have been identified, little is known about the signals controlling lineage decisions of the two cell types. Here, we show by conditionally deleting beta-catenin in limb and head mesenchyme that beta-catenin is required for osteoblast lineage differentiation. Osteoblast precursors lacking beta-catenin are blocked in differentiation and develop into chondrocytes instead. In vitro experiments demonstrate that this is a cell-autonomous function of beta-catenin in an osteoblast precursor. Furthermore, detailed in vivo and in vitro loss- and gain-of-function analyses reveal that beta-catenin activity is necessary and sufficient to repress the differentiation of mesenchymal cells into Runx2- and Sox9-positive skeletal precursors. Thus, canonical Wnt/beta-catenin signaling is essential for skeletal lineage differentiation, preventing transdifferentiation of osteoblastic cells into chondrocytes.
authors.affiliation: Research Institute for Molecular Pathology, Vienna, Austria.
authors.forename: Theo P
authors.initials: TP
authors.lastname: Hill
authors.forename: Daniela
authors.initials: D
authors.lastname: Später
authors.forename: Makoto M
authors.initials: MM
authors.lastname: Taketo
authors.forename: Walter
authors.initials: W
authors.lastname: Birchmeier
authors.forename: Christine
authors.initials: C
authors.lastname: Hartmann
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology* / Q000502:physiology*; D020219:Chondrogenesis; D050659:Core Binding Factor Alpha 1 Subunit; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008648:Mesoderm / Q000166:cytology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009154:Mutation; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology*; D010012:Osteogenesis; D055758:SOX9 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics; D051153:Wnt Proteins; D051176:beta Catenin
chemical_list: C495267:CTNNB1 protein, mouse; D050659:Core Binding Factor Alpha 1 Subunit; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D036341:Intercellular Signaling Peptides and Proteins; C493716:Runx2 protein, mouse; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D015534:Trans-Activators; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin