title: Distinct requirements for cranial ectoderm and mesenchyme-derived wnts in specification and differentiation of osteoblast and dermal progenitors.
abstract: The cranial bones and dermis differentiate from mesenchyme beneath the surface ectoderm. Fate selection in cranial mesenchyme requires the canonical Wnt effector molecule β-catenin, but the relative contribution of Wnt ligand sources in this process remains unknown. Here we show Wnt ligands are expressed in cranial surface ectoderm and underlying supraorbital mesenchyme during dermal and osteoblast fate selection. Using conditional genetics, we eliminate secretion of all Wnt ligands from cranial surface ectoderm or undifferentiated mesenchyme, to uncover distinct roles for ectoderm- and mesenchyme-derived Wnts. Ectoderm Wnt ligands induce osteoblast and dermal fibroblast progenitor specification while initiating expression of a subset of mesenchymal Wnts. Mesenchyme Wnt ligands are subsequently essential during differentiation of dermal and osteoblast progenitors. Finally, ectoderm-derived Wnt ligands provide an inductive cue to the cranial mesenchyme for the fate selection of dermal fibroblast and osteoblast lineages. Thus two sources of Wnt ligands perform distinct functions during osteoblast and dermal fibroblast formation.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: L Henry
authors.initials: LH
authors.lastname: Goodnough
authors.affiliation: Department of Biology, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Gregg J
authors.initials: GJ
authors.lastname: Dinuoscio
authors.affiliation: Department of Biology, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: James W
authors.initials: JW
authors.lastname: Ferguson
authors.affiliation: Department of Craniofacial Biology, University of Colorado School of Dental Medicine, Aurora, Colorado, United States of America.
authors.forename: Trevor
authors.initials: T
authors.lastname: Williams
authors.affiliation: Visual Systems Group, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lang
authors.affiliation: Department of Biology, Case Western Reserve University, Cleveland, Ohio, United States of America ; Department of Genetics, Case Western Reserve University, Cleveland, Ohio, United States of America ; Department of Dermatology Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Radhika P
authors.initials: RP
authors.lastname: Atit
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D004475:Ectoderm / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008024:Ligands; D008648:Mesoderm / Q000166:cytology / Q000254:growth & development; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D012886:Skull / Q000254:growth & development* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D008024:Ligands; D051153:Wnt Proteins; D051176:beta Catenin