title: Twist1 mediates repression of chondrogenesis by β-catenin to promote cranial bone progenitor specification.
abstract: The bones of the mammalian skull vault form through intramembranous ossification. Skull bones ossify directly, in a process regulated by β-catenin, instead of passing through a cartilage intermediate. We tested whether β-catenin is necessary for fate selection of intramembranous bone progenitors in the skull. Here, we show in mice that removal of β-catenin from skull bone progenitors results in the near complete transformation of the skull bones to cartilage, whereas constitutive β-catenin activation inhibits skull bone fate selection. β-catenin directly activated Twist1 expression in skull progenitors, conditional Twist1 deletion partially phenocopied the absence of β-catenin, and Twist1 deletion partially restored bone formation in the presence of constitutive β-catenin activation. Finally, Twist1 bound robustly to the 3'UTR of Sox9, the central initiator of chondrogenesis, suggesting that Twist1 might directly repress cartilage formation through Sox9. These findings provide insight into how β-catenin signaling via Twist1 actively suppresses the formation of cartilage and promotes intramembranous ossification in the skull.
authors.affiliation: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106,  USA.
authors.forename: L Henry
authors.initials: LH
authors.lastname: Goodnough
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chang
authors.forename: Charles
authors.initials: C
authors.lastname: Treloar
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Peter C
authors.initials: PC
authors.lastname: Scacheri
authors.forename: Radhika P
authors.initials: RP
authors.lastname: Atit
mesh_terms: D000818:Animals; D001846:Bone Development; D002356:Cartilage / Q000166:cytology; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D020219:Chondrogenesis; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis; D011401:Promoter Regions, Genetic; D055758:SOX9 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D012886:Skull / Q000166:cytology* / Q000196:embryology*; D013234:Stem Cells / Q000502:physiology*; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D051879:Twist-Related Protein 1; D051176:beta Catenin; C067250:Twist1 protein, mouse