ZBTB20 is Essential for Cochlear Maturation and Hearing in Mice

Xie, Z.; Ma, X.; Bai, Q.; Tang, J.; Sun, J.; Jiang, F.; Guo, W.; Wang, C.; Yang, R.; Wen, Y.; Wang, F.; Chen, Y.; Zhang, H.; He, D. Z.; Kelley, M. W.; Yang, S.; Zhang, W. J.

doi:10.1101/2022.12.23.521726

bioRxiv · 10.1101/2022.12.23.521726

ZBTB20 is Essential for Cochlear Maturation and Hearing in Mice

Xie, Z.·Ma, X.·Bai, Q.·Tang, J.·Sun, J.·Jiang, F.·Guo, W.·Wang, C.·Yang, R.·Wen, Y.·Wang, F.·Chen, Y.·Zhang, H.·He, D. Z.·Kelley, M. W.·Yang, S.·Zhang, W. J.

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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 non-sensory 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 non-sensory 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, a flattened spiral prominence, and a lack of identifiable Boettcher cells. Furthermore, these defects are related with a failure in the terminal differentiation of the non-sensory epithelium covering the outer border Claudius cells, outer sulcus root cells and spiral prominence epithelial cells. Transcriptome analysis shows ZBTB20 regulates genes coding for tectorial membrane proteins in the greater epithelial ridge, and those preferentially expressed in root cells and spiral prominence epithelium. Our results point to ZBTB20 as an essential regulator for postnatal cochlear maturation and particularly for the terminal differentiation of cochlear lateral non-sensory domain.

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Xie, Z., Ma, X., Bai, Q., Tang, J., Sun, J., Jiang, F., Guo, W., Wang, C., Yang, R., Wen, Y., Wang, F., Chen, Y., Zhang, H., He, D. Z., Kelley, M. W., Yang, S., Zhang, W. J.. 2022-12-23. ZBTB20 is Essential for Cochlear Maturation and Hearing in Mice. https://doi.org/10.1101/2022.12.23.521726

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