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

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  • Taha Adnan Jan
    Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Renjie Chai
    Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Zahra Nabi Sayyid
    Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Renée van Amerongen
    Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Anping Xia
    Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Tian Wang
    Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Saku Tapani Sinkkonen
    Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Yi Arial Zeng
    Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Jared Ruben Levin
    Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Stefan Heller
    Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Roel Nusse
    Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Alan Gi-Lun Cheng
    Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.

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<jats:p>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.</jats:p>

Journal

  • Development

    Development 140 (6), 1196-1206, 2013-03-15

    The Company of Biologists

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