Tympanic border cells are Wnt-responsive and can act as progenitors for postnatal mouse cochlear cells

Taha Adnan Jan, Renjie Chai, Zahra Nabi Sayyid, Renée van Amerongen, Anping Xia, Tian Wang, Saku Tapani Sinkkonen, Yi Arial Zeng, Jared Ruben Levin, Stefan Heller, Roel Nusse, Alan Gi Lun Cheng

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Permanent hearing loss is caused by the irreversible damage of cochlear sensory hair cells and nonsensory supporting cells. In the postnatal cochlea, the sensory epithelium is terminally differentiated, whereas tympanic border cells (TBCs) beneath the sensory epithelium are proliferative. The functions of TBCs are poorly characterized. Using an Axin2lacZ Wnt reporter mouse, we found transient but robust Wnt signaling and proliferation in TBCs during the first 3 postnatal weeks, when the number of TBCs decreases. In vivo lineage tracing shows that a subset of hair cells and supporting cells is derived postnatally from Axin2-expressing TBCs. In cochlear explants, Wnt agonists stimulated the proliferation of TBCs, whereas Wnt inhibitors suppressed it. In addition, purified Axin2lacZ cells were clonogenic and self-renewing in culture in a Wnt-dependent manner, and were able to differentiate into hair cell-like and supporting cell-like cells. Taken together, our data indicate that Axin2-positive TBCs are Wnt responsive and can act as precursors to sensory epithelial cells in the postnatal cochlea.

Original languageEnglish
Pages (from-to)1196-1206
Number of pages11
JournalDevelopment (Cambridge)
Volume140
Issue number6
DOIs
StatePublished - Mar 15 2013

Keywords

  • Development
  • Hair cells
  • Inner ear
  • Mouse
  • Regeneration
  • Stem cells
  • β-catenin

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