title: Twist1 contributes to cranial bone initiation and dermal condensation by maintaining Wnt signaling responsiveness.
abstract: BACKGROUND
  Specification of cranial bone and dermal fibroblast progenitors in the supraorbital arch mesenchyme is Wnt/β-catenin signaling-dependent. The mechanism underlying how these cells interpret instructive signaling cues and differentiate into these two lineages is unclear. Twist1 is a target of the Wnt/β-catenin signaling pathway and is expressed in cranial bone and dermal lineages.
  
  
  RESULTS
  Here, we show that onset of Twist1 expression in the mouse cranial mesenchyme is dependent on ectodermal Wnts and mesenchymal β-catenin activity. Conditional deletion of Twist1 in the supraorbital arch mesenchyme leads to cranial bone agenesis and hypoplastic dermis, as well as craniofacial malformation of eyes and palate. Twist1 is preferentially required for cranial bone lineage commitment by maintaining Wnt responsiveness. In the conditional absence of Twist1, the cranial dermis fails to condense and expand apically leading to extensive cranial dermal hypoplasia with few and undifferentiated hair follicles.
  
  
  CONCLUSIONS
  Thus, Twist1, a target of canonical Wnt/β-catenin signaling, also functions to maintain Wnt responsiveness and is a key effector for cranial bone fate selection and dermal condensation.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio.
authors.forename: L Henry
authors.initials: LH
authors.lastname: Goodnough
authors.affiliation: Department of Biology, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Gregg J
authors.initials: GJ
authors.lastname: Dinuoscio
authors.affiliation: Department of Biology, Case Western Reserve University, Cleveland, Ohio.|Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio.|Department of Dermatology, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Radhika P
authors.initials: RP
authors.lastname: Atit
mesh_terms: D000818:Animals; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018859:Hair Follicle / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012886:Skull / Q000196:embryology* / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D051879:Twist-Related Protein 1; D051153:Wnt Proteins; D051176:beta Catenin; C067250:Twist1 protein, mouse
keywords: craniofacial development; skin; skull bone