title: Spatial and Age-Dependent Hair Cell Generation in the Postnatal Mammalian Utricle.
abstract: Loss of vestibular hair cells is a common cause of balance disorders. Current treatment options for bilateral vestibular dysfunction are limited. During development, atonal homolog 1 (Atoh1) is sufficient and necessary for the formation of hair cells and provides a promising gene target to induce hair cell generation in the mammals. In this study, we used a transgenic mouse line to test the age and cell type specificity of hair cell induction in the postnatal utricle in mice. We found that forced Atoh1 expression in vivo can induce hair cell formation in the utricle from postnatal days 1 to 21, while the efficacy of hair cell induction is progressively reduced as the animals become older. In the utricle, the induction of hair cells occurs both within the sensory region and in cells in the transitional epithelium next to the sensory region. Within the sensory epithelium, the central region, known as the striola, is most subjective to the induction of hair cell formation. Furthermore, forced Atoh1 expression can promote proliferation in an age-dependent manner that mirrors the progressively reduced efficacy of hair cell induction in the postnatal utricle. These results suggest that targeting both cell proliferation and Atoh1 in the utricle striolar region may be explored to induce hair cell regeneration in mammals. The study also demonstrates the usefulness of the animal model that provides an in vivo Atoh1 induction model for vestibular regeneration studies.
authors: Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, 30322, USA.|Department of Otology and Skull Base Surgery, Eye and ENT Hospital, Fudan University, Shanghai, 200031, China.
authors: Zhen
authors: Z
authors: Gao
authors: Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, 30322, USA.
authors: Michael C
authors: MC
authors: Kelly
authors: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital and Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Dehong
authors: D
authors: Yu
authors: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital and Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Hao
authors: H
authors: Wu
authors: Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, 30322, USA.|Department of Otolaryngology, Emory University School of Medicine, Atlanta, Georgia, 30322, USA.
authors: Xi
authors: X
authors: Lin
authors: Department of Otology and Skull Base Surgery, Eye and ENT Hospital, Fudan University, Shanghai, 200031, China. chifanglu@126.com.
authors: Fang-Lu
authors: FL
authors: Chi
authors: Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, 30322, USA. ping.chen@emory.edu.
authors: Ping
authors: P
authors: Chen
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology; D002455:Cell Division; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006198:Hair Cells, Auditory / Q000166:cytology*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012038:Regeneration; D012444:Saccule and Utricle / Q000166:cytology* / Q000254:growth & development; D019076:Transgenes
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004318:Doxycycline; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C500943:Atoh1 protein, mouse
keywords: Atoh1; Hair cell; Proliferation; Regeneration; Utricle; Vestibule