title: Tympanic border cells are Wnt-responsive and can act as progenitors for postnatal mouse cochlear cells.
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 Axin2(lacZ) 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 Axin2(lacZ) 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.
authors: Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors: Taha Adnan
authors: TA
authors: Jan
authors: Renjie
authors: R
authors: Chai
authors: Zahra Nabi
authors: ZN
authors: Sayyid
authors: Renée
authors: R
authors: van Amerongen
authors: Anping
authors: A
authors: Xia
authors: Tian
authors: T
authors: Wang
authors: Saku Tapani
authors: ST
authors: Sinkkonen
authors: Yi Arial
authors: YA
authors: Zeng
authors: Jared Ruben
authors: JR
authors: Levin
authors: Stefan
authors: S
authors: Heller
authors: Roel
authors: R
authors: Nusse
authors: Alan Gi-Lun
authors: AG
authors: Cheng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002645:Chickens; D003051:Cochlea / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D004432:Ear, Middle / Q000166:cytology* / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology*
chemical_list: D060466:Axin Protein; C111729:Axin2 protein, mouse