Canonical Wnt signaling promotes the proliferation and neurogenesis of peripheral olfactory stem cells during postnatal development and adult regeneration

Ya Zhou Wang, Takashi Yamagami, Qini Gan, Yongping Wang, Tianyu Zhao, Salaheddin Hamad, Paul Lott, Nikolai Schnittke, James E. Schwob, Chengji Zhou

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1553-1563
Number of pages11
JournalJournal of Cell Science
Volume124
Issue number9
DOIs
StatePublished - May 1 2011

Fingerprint

Olfactory Mucosa
Neurogenesis
Regeneration
Wnt Signaling Pathway
Stem Cells
Olfactory Receptor Neurons
Peripheral Blood Stem Cells
Cell Lineage
Transgenic Mice
Epithelial Cells

Keywords

  • Neurogenesis
  • Olfactory epithelial stem cells
  • Regeneration
  • Sox2
  • Wnt

ASJC Scopus subject areas

  • Cell Biology

Cite this

Canonical Wnt signaling promotes the proliferation and neurogenesis of peripheral olfactory stem cells during postnatal development and adult regeneration. / Wang, Ya Zhou; Yamagami, Takashi; Gan, Qini; Wang, Yongping; Zhao, Tianyu; Hamad, Salaheddin; Lott, Paul; Schnittke, Nikolai; Schwob, James E.; Zhou, Chengji.

In: Journal of Cell Science, Vol. 124, No. 9, 01.05.2011, p. 1553-1563.

Research output: Contribution to journalArticle

Wang, Ya Zhou ; Yamagami, Takashi ; Gan, Qini ; Wang, Yongping ; Zhao, Tianyu ; Hamad, Salaheddin ; Lott, Paul ; Schnittke, Nikolai ; Schwob, James E. ; Zhou, Chengji. / Canonical Wnt signaling promotes the proliferation and neurogenesis of peripheral olfactory stem cells during postnatal development and adult regeneration. In: Journal of Cell Science. 2011 ; Vol. 124, No. 9. pp. 1553-1563.
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