title: Canonical Wnt signaling promotes the proliferation and neurogenesis of peripheral olfactory stem cells during postnatal development and adult regeneration.
abstract: The mammalian olfactory epithelium (OE) has a unique stem cell or progenitor niche, which is responsible for the constant peripheral neurogenesis throughout the lifespan of the animal. However, neither the signals that regulate the behavior of these cells nor the lineage properties of the OE stem cells are well understood. Multiple Wnt signaling components exhibit dynamic expression patterns in the developing OE. We generated Wnt signaling reporter TOPeGFP transgenic mice and found TOPeGFP activation predominantly in proliferating Sox2(+) OE basal cells during early postnatal development. FACS-isolated TOPeGFP(+) OE basal cells are required, but are not sufficient, for formation of spheres. Wnt3a significantly promotes the proliferation of the Sox2(+) OE sphere cells. Wnt-stimulated OE sphere cells maintain their multipotency and can differentiate into most types of neuronal and non-neuronal epithelial cells. Also, Wnt activators shift the production of differentiated cells toward olfactory sensory neurons. Moreover, TOPeGFP(+) cells are robustly increased in the adult OE after injury. In vivo administration of Wnt modulators significantly alters the regeneration potential. This study demonstrates the role of the canonical Wnt signaling pathway in the regulation of OE stem cells or progenitors during development and regeneration.
authors.affiliation: Department of Cell Biology and Human Anatomy, University of California, Davis, CA 95616, USA.
authors.forename: Ya-Zhou
authors.initials: YZ
authors.lastname: Wang
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamagami
authors.forename: Qini
authors.initials: Q
authors.lastname: Gan
authors.forename: Yongping
authors.initials: Y
authors.lastname: Wang
authors.forename: Tianyu
authors.initials: T
authors.lastname: Zhao
authors.forename: Salaheddin
authors.initials: S
authors.lastname: Hamad
authors.forename: Paul
authors.initials: P
authors.lastname: Lott
authors.forename: Nikolai
authors.initials: N
authors.lastname: Schnittke
authors.forename: James E
authors.initials: JE
authors.lastname: Schwob
authors.forename: Chengji J
authors.initials: CJ
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009831:Olfactory Mucosa / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013234:Stem Cells / Q000166:cytology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060508:Wnt3 Protein; D060509:Wnt3A Protein
chemical_list: D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse