title: Wnts produced by Osterix-expressing osteolineage cells regulate their proliferation and differentiation.
abstract: Wnt signaling is a critical regulator of bone development, but the identity and role of the Wnt-producing cells are still unclear. We addressed these questions through in situ hybridization, lineage tracing, and genetic experiments. First, we surveyed the expression of all 19 Wnt genes and Wnt target gene Axin2 in the neonatal mouse bone by in situ hybridization, and demonstrated--to our knowledge for the first time--that Osterix-expressing cells coexpress Wnt and Axin2. To track the behavior and cell fate of Axin2-expressing osteolineage cells, we performed lineage tracing and showed that they sustain bone formation over the long term. Finally, to examine the role of Wnts produced by Osterix-expressing cells, we inhibited Wnt secretion in vivo, and observed inappropriate differentiation, impaired proliferation, and diminished Wnt signaling response. Therefore, Osterix-expressing cells produce their own Wnts that in turn induce Wnt signaling response, thereby regulating their proliferation and differentiation.
authors.affiliation: Program in Cancer Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305.
authors.forename: Si Hui
authors.initials: SH
authors.lastname: Tan
authors.affiliation: Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery.
authors.forename: Kshemendra
authors.initials: K
authors.lastname: Senarath-Yapa
authors.affiliation: Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Chung
authors.affiliation: Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
authors.affiliation: Division of Endocrinology.
authors.forename: Joy Y
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305 Department of Developmental Biology, Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, and rnusse@stanford.edu.
authors.forename: Roeland
authors.initials: R
authors.lastname: Nusse
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D060466:Axin Protein / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002469:Cell Separation; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010012:Osteogenesis / Q000502:physiology; D010641:Phenotype; D016133:Polymerase Chain Reaction; D000076182:Sp7 Transcription Factor; D013234:Stem Cells; D014157:Transcription Factors / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; C111729:Axin2 protein, mouse; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; C486030:Sost protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D051153:Wnt Proteins
keywords: Osterix; Wnt; Wntless; bone; development