title: Wntless spatially regulates bone development through β-catenin-dependent and independent mechanisms.
abstract: BACKGROUND
  Canonical and noncanonical Wnt signaling pathways both play pivotal roles in bone development. Wntless/GPR177 is a chaperone protein that is required for secretion of all Wnt ligands. We previously showed that deletion of Wntless within mature osteoblasts severely impaired postnatal bone homeostasis.
  
  
  RESULTS
  In this study, we systemically evaluated how deletion of Wntless in different stages of osteochondral differentiation affected embryonic bone development, by crossing Wntless (Wls)-flox/flox mice with strains expressing cre recombinase behind the following promoters: Osteocalcin, Collagen 2a1, or Dermo1. Ex vivo µCT and whole-mount skeletal staining were performed to examine skeletal mineralization. Histology and immunohistochemistry were used to evaluate cellular differentiation and alterations in Wnt signaling. In this work, we found that Wntless regulated chondrogenesis and osteogenesis through both canonical and noncanonical Wnt signaling.
  
  
  CONCLUSIONS
  These findings provide more insight into the requirements of different Wnt-secretion cell types critical for skeletal development.
authors.affiliation: Program for Skeletal Disease and Tumor Microenvironment and Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan.
authors.forename: Zhendong A
authors.initials: ZA
authors.lastname: Zhong
authors.affiliation: Program for Skeletal Disease and Tumor Microenvironment and Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan.
authors.forename: Juraj
authors.initials: J
authors.lastname: Zahatnansky
authors.affiliation: Program for Skeletal Disease and Tumor Microenvironment and Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan.
authors.forename: John
authors.initials: J
authors.lastname: Snider
authors.affiliation: Program for Skeletal Disease and Tumor Microenvironment and Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan.
authors.forename: Emily
authors.initials: E
authors.lastname: Van Wieren
authors.affiliation: Program for Skeletal Disease and Tumor Microenvironment and Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan.
authors.forename: Cassandra R
authors.initials: CR
authors.lastname: Diegel
authors.affiliation: Program for Skeletal Disease and Tumor Microenvironment and Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan.
authors.forename: Bart O
authors.initials: BO
authors.lastname: Williams
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000196:embryology* / Q000378:metabolism; D002113:Calcification, Physiologic; D019902:Chondrocytes / Q000502:physiology; D020219:Chondrogenesis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008024:Ligands; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis; D011401:Promoter Regions, Genetic; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C545200:Gpr177 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D051153:Wnt Proteins; D051176:beta Catenin
keywords: Col2a1; Dermo1; Osteocalcin; Wnt secretion; Wntless; skeletal development