title: Jxc1/Sobp, encoding a nuclear zinc finger protein, is critical for cochlear growth, cell fate, and patterning of the organ of corti.
abstract: The mouse cochlea emerges from the ventral pole of the otocyst to form a one and three-quarter coil. Little is known about the factors that control the growth of the cochlea. Jackson circler (jc) is a recessive mutation causing deafness resulting from a growth arrest of the cochlea duct at day 13.5 of embryonic development. Here, we identify the vertebrate homolog of the Drosophila Sobp (sine oculis-binding protein) gene (named Jxc1) in the jc locus. Jxc1 encodes a nuclear protein that has two FCS-type zinc finger domains (PS51024) and bears nuclear localization signals and highly conserved sequence motifs. Transiently expressed wild-type protein is targeted to the nucleus, but mutant isoforms were mislocalized in the cytoplasm. In jc mutants, the cellular patterning of the organ of Corti is severely disrupted, exhibiting supernumerary hair cells at the apex, showing mirror-image duplications of tunnel of Corti and inner hair cells, and expressing ectopic vestibular-like hair cells within Kölliker's organ. Jxc1 mRNA was detected in inner ear sensory hair cells, supporting cells, and the acoustic ganglia. Expression was also found in the developing retina, olfactory epithelium, trigeminal ganglion, and hair follicles. Collectively, our data support a role for Jxc1 in controlling a critical step in cochlear growth, cell fate, and patterning of the organ of Corti.
authors.affiliation: Sections on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland 20850, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
authors.forename: Mireille
authors.initials: M
authors.lastname: Montcouquiol
authors.forename: Rene
authors.initials: R
authors.lastname: Calderon
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Jenkins
authors.forename: Neal G
authors.initials: NG
authors.lastname: Copeland
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Kelley
authors.forename: Konrad
authors.initials: K
authors.lastname: Noben-Trauth
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D003051:Cochlea / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006198:Hair Cells, Auditory / Q000166:cytology / Q000378:metabolism; D008667:Metalloproteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D019913:Nuclear Localization Signals / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D009925:Organ of Corti / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013136:Spiral Ganglion / Q000166:cytology / Q000196:embryology / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C530505:Jxc1 protein, mouse; D008667:Metalloproteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D012333:RNA, Messenger; C103175:Sob protein, Drosophila