Jxc1/Sobp, encoding a nuclear zinc finger protein, is critical for cochlear growth, cell fate, and patterning of the organ of corti
Jxc1/Sobp, encoding a nuclear zinc finger protein, is critical for cochlear growth, cell fate, and patterning of the organ of corti
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DOI：
10.1523/jneurosci.1280-08.2008
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发表时间：
2008-06-25
影响因子：
5.3
通讯作者：
Noben-Trauth, Konrad
中科院分区：
文献类型：
--
作者：
Chen, Zheng;Montcouquiol, Mireille;Noben-Trauth, Konrad
小鼠耳蜗从耳囊的腹极伸出，形成一个又四分之三的线圈。人们对控制耳蜗生长的因素知之甚少。 Jackson Circler (jc) 是一种隐性突变，由于胚胎发育第 13.5 天时耳蜗管生长停滞而导致耳聋。在这里，我们鉴定了 jc 位点中果蝇 Sobp（正弦眼结合蛋白）基因（名为 Jxc1）的脊椎动物同源物。 Jxc1 编码具有两个 FCS 型锌指结构域 (PS51024) 的核蛋白，并具有核定位信号和高度保守的序列基序。瞬时表达的野生型蛋白靶向细胞核，但突变同种型错误定位在细胞质中。在 jc 突变体中，柯蒂氏器官的细胞模式被严重破坏，在顶端显示出多余的毛细胞，显示出柯蒂氏隧道和内毛细胞的镜像重复，并在科利克器官内表达异位前庭样毛细胞。在内耳感觉毛细胞、支持细胞和听神经节中检测到 Jxc1 mRNA。在发育中的视网膜、嗅觉上皮、三叉神经节和毛囊中也发现了表达。总的来说，我们的数据支持 Jxc1 在控制耳蜗生长、细胞命运和柯蒂氏器模式的关键步骤中的作用。
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 Kolliker'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.