TY - JOUR
T1 - Jxc1/Sobp, encoding a nuclear zinc finger protein, is critical for cochlear growth, cell fate, and patterning of the organ of corti
AU - Chen, Zheng
AU - Montcouquiol, Mireille
AU - Calderon, Rene
AU - Jenkins, Nancy A.
AU - Copeland, Neal G.
AU - Kelley, Matthew W.
AU - Noben-Trauth, Konrad
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2008/6/25
Y1 - 2008/6/25
N2 - 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.
AB - 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.
KW - Cochlea dysplasia
KW - FCS zinc finger
KW - Jackson circler
KW - Jxc1
KW - Kölliker's organ
KW - Organ of corti
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U2 - 10.1523/JNEUROSCI.1280-08.2008
DO - 10.1523/JNEUROSCI.1280-08.2008
M3 - Article
C2 - 18579736
AN - SCOPUS:48549084248
VL - 28
SP - 6633
EP - 6641
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 26
ER -