PDF(Pubmed)
Abstract：
The mammalian cochlear epithelium undergoes substantial remodeling and maturation before the onset of hearing. However, very little is known about the transcriptional network governing cochlear late-stage maturation and particularly the differentiation of its lateral nonsensory region. Here, we establish ZBTB20 as an essential transcription factor required for cochlear terminal differentiation and maturation and hearing. ZBTB20 is abundantly expressed in the developing and mature cochlear nonsensory epithelial cells, with transient expression in immature hair cells and spiral ganglion neurons. Otocyst-specific deletion of Zbtb20 causes profound deafness with reduced endolymph potential in mice. The subtypes of cochlear epithelial cells are normally generated, but their postnatal development is arrested in the absence of ZBTB20, as manifested by an immature appearance of the organ of Corti, malformation of tectorial membrane (TM), a flattened spiral prominence (SP), and a lack of identifiable Boettcher cells. Furthermore, these defects are related with a failure in the terminal differentiation of the nonsensory epithelium covering the outer border Claudius cells, outer sulcus root cells, and SP epithelial cells. Transcriptome analysis shows that ZBTB20 regulates genes encoding for TM proteins in the greater epithelial ridge, and those preferentially expressed in root cells and SP epithelium. Our results point to ZBTB20 as an essential regulator for postnatal cochlear maturation and particularly for the terminal differentiation of cochlear lateral nonsensory domain.
摘要：
哺乳动物耳蜗上皮在听力开始之前经历了实质性的重塑和成熟。然而,关于控制耳蜗后期成熟的转录网络，尤其是其横向非感觉区域的分化，知之甚少。这里,我们将ZBTB20确立为耳蜗终末分化，成熟和听力所需的必需转录因子。ZBTB20在发育中和成熟的耳蜗非感觉上皮细胞中大量表达，在未成熟的毛细胞和螺旋神经节神经元中瞬时表达。Zbtb20的耳囊肿特异性缺失会导致深度耳聋，并降低小鼠的内淋巴潜能。耳蜗上皮细胞的亚型是正常产生的，但是他们的产后发育在没有ZBTB20的情况下被阻止，表现为Corti器官的不成熟外观，膜(TM)畸形，扁平螺旋突起(SP)，缺乏可识别的Boettcher细胞。此外，这些缺陷与覆盖外边界克劳迪斯细胞的非感觉上皮的终末分化失败有关，外沟根细胞，和SP上皮细胞。转录组分析表明，ZBTB20调节编码大上皮脊TM蛋白的基因，以及在根细胞和SP上皮中优先表达的那些。我们的结果表明ZBTB20是出生后耳蜗成熟的重要调节因子，尤其是耳蜗外侧非感觉域的终末分化。
