title: Canonical Wnt Signaling Drives Tumor-Like Lesions from Sox2-Positive Precursors of the Murine Olfactory Epithelium.
abstract: Canonical Wnt signaling is known to promote proliferation of olfactory stem cells. In order to investigate the effects of a constitutive activation of Wnt signaling in Sox2-positive precursor cells of the olfactory epithelium, we used transgenic mice that allowed an inducible deletion of exon 3 of the Ctnnb1 gene, which is responsible for the phosphorylation and degradation of Ctnnb1 protein. After induction of aberrant Wnt activation by Ctnnb1 deletion at embryonic day 14, such mice developed tumor-like lesions in upper parts of the nasal cavity. We still observed areas of epithelial hyperplasia within the olfactory epithelium following early postnatal Wnt activation, but the olfactory epithelial architecture remained unaffected in most parts when Wnt was activated at postnatal day 21 or later. In summary, our results suggest an age-dependent tumorigenic potential of aberrant Wnt signaling in the olfactory epithelium of mice.
authors.affiliation: Center for Neuropathology, Ludwig-Maximilians-University, Munich, Germany.|Department of Internal Medicine II, University Medical Center, Hamburg-Eppendorf, Germany.
authors.forename: Nils W
authors.initials: NW
authors.lastname: Engel
authors.affiliation: Center for Neuropathology, Ludwig-Maximilians-University, Munich, Germany.|Institute of Neuropathology, University Medical Center, Hamburg-Eppendorf, Germany.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Neumann
authors.affiliation: Center for Neuropathology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Ahlfeld
authors.affiliation: Center for Neuropathology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Annika K
authors.initials: AK
authors.lastname: Wefers
authors.affiliation: Center for Neuropathology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Merk
authors.affiliation: Center for Neuropathology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Ohli
authors.affiliation: Center for Neuropathology, Ludwig-Maximilians-University, Munich, Germany.|Institute of Neuropathology, University Medical Center, Hamburg-Eppendorf, Germany.|Research Institute Children's Cancer Center, Hamburg, Germany.|Department of Pediatric Hematology and Oncology, University Medical Center, Hamburg-Eppendorf, Germany.
authors.forename: Ulrich
authors.identifier: http://orcid.org/0000-0002-8731-1121
authors.initials: U
authors.lastname: Schüller
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004789:Enzyme Activation; D005260:Female; D006965:Hyperplasia / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009669:Nose Neoplasms / Q000235:genetics*; D009831:Olfactory Mucosa / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C495267:CTNNB1 protein, mouse; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D051153:Wnt Proteins; D051176:beta Catenin; D013629:Tamoxifen