title: β-Catenin is required for hair-cell differentiation in the cochlea.
abstract: The development of hair cells in the auditory system can be separated into steps; first, the establishment of progenitors for the sensory epithelium, and second, the differentiation of hair cells. Although the differentiation of hair cells is known to require the expression of basic helix-loop-helix transcription factor, Atoh1, the control of cell proliferation in the region of the developing cochlea that will ultimately become the sensory epithelium and the cues that initiate Atoh1 expression remain obscure. We assessed the role of Wnt/β-catenin in both steps in gain- and loss-of-function models in mice. The canonical Wnt pathway mediator, β-catenin, controls the expression of Atoh1. Knock-out of β-catenin inhibited hair-cell, as well as pillar-cell, differentiation from sensory progenitors but was not required to maintain a hair-cell fate once specified. Constitutive activation of β-catenin expanded sensory progenitors by inducing additional cell division and resulted in the differentiation of extra hair cells. Our data demonstrate that β-catenin plays a role in cell division and differentiation in the cochlear sensory epithelium.
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02115, Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts 02114, Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China, Department of Surgery, University of California San Diego, La Jolla, California, Department of Otolaryngology, Head and Neck Surgery, University of Toronto, Toronto, Canada, Biological Sciences, Sunnybrook Research Institute, Sunnybrook Health Sciences Center, Toronto, Canada, and Program in Speech and Hearing Bioscience and Technology, Division of Health Sciences and Technology, Harvard and MIT, Cambridge, Massachusetts 02139.
authors.forename: Fuxin
authors.initials: F
authors.lastname: Shi
authors.forename: Lingxiang
authors.initials: L
authors.lastname: Hu
authors.forename: Bonnie E
authors.initials: BE
authors.lastname: Jacques
authors.forename: Joanna F
authors.initials: JF
authors.lastname: Mulvaney
authors.forename: Alain
authors.initials: A
authors.lastname: Dabdoub
authors.forename: Albert S B
authors.initials: AS
authors.lastname: Edge
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology; D015820:Cadherins / Q000235:genetics / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D003051:Cochlea / Q000166:cytology / Q000502:physiology*; D004848:Epithelium / Q000294:innervation / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006199:Hair Cells, Auditory, Inner / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009925:Organ of Corti / Q000254:growth & development / Q000502:physiology; D013234:Stem Cells / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology; D051176:beta Catenin / Q000502:physiology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015820:Cadherins; D051153:Wnt Proteins; D051176:beta Catenin; C500943:Atoh1 protein, mouse