title: LMO4 functions as a negative regulator of sensory organ formation in the mammalian cochlea.
abstract: In mammals, formation of the auditory sensory organ (the organ of Corti) is restricted to a specialized area of the cochlea. However, the molecular mechanisms limiting sensory formation to this discrete region in the ventral cochlear duct are not well understood, nor is it known whether other regions of the cochlea have the competence to form the organ of Corti. Here we identify LMO4, a LIM-domain-only nuclear protein, as a negative regulator of sensory organ formation in the cochlea. Inactivation of Lmo4 in mice leads to an ectopic organ of Corti (eOC) located in the lateral cochlea. The eOC retains the features of the native organ, including inner and outer hair cells, supporting cells, and other nonsensory specialized cell types. However, the eOC shows an orientation opposite to the native organ, such that the eOC appears as a mirror-image duplication to the native organ of Corti. These data demonstrate a novel sensory competent region in the lateral cochlear duct that is regulated by LMO4 and may be amenable to therapeutic manipulation.
authors: Flaum Eye Institute and Department of Ophthalmology, University of Rochester, Rochester, New York 14642.
authors: Min
authors: M
authors: Deng
authors: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China.
authors: Xiong-jian
authors: XJ
authors: Luo
authors: Flaum Eye Institute and Department of Ophthalmology, University of Rochester, Rochester, New York 14642.
authors: Ling
authors: L
authors: Pan
authors: Flaum Eye Institute and Department of Ophthalmology, University of Rochester, Rochester, New York 14642.
authors: Hua
authors: H
authors: Yang
authors: Flaum Eye Institute and Department of Ophthalmology, University of Rochester, Rochester, New York 14642.
authors: Xiaoling
authors: X
authors: Xie
authors: College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China, and.
authors: Guoqing
authors: G
authors: Liang
authors: Flaum Eye Institute and Department of Ophthalmology, University of Rochester, Rochester, New York 14642, Gannan Medical University, Ganzhou, Jiangxi 341000, China.
authors: Liang
authors: L
authors: Huang
authors: Flaum Eye Institute and Department of Ophthalmology, University of Rochester, Rochester, New York 14642, Gannan Medical University, Ganzhou, Jiangxi 341000, China.
authors: Fang
authors: F
authors: Hu
authors: Flaum Eye Institute and Department of Ophthalmology, University of Rochester, Rochester, New York 14642.
authors: Amy E
authors: AE
authors: Kiernan
authors: Flaum Eye Institute and Department of Ophthalmology, University of Rochester, Rochester, New York 14642, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 310036, China, and lin_gan@urmc.rochester.edu.
authors: Lin
authors: L
authors: Gan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D000818:Animals; D003051:Cochlea / Q000254:growth & development; D005260:Female; D055879:Gene Knock-In Techniques; D060588:LIM Domain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009925:Organ of Corti / Q000254:growth & development*; D012679:Sense Organs / Q000254:growth & development
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; C491976:Lmo4 protein, mouse
keywords: LIM-domain; LMO4; cochlea; inner ear development; organ of Corti; transcriptional regulator