Six1 is essential for differentiation and patterning of the mammalian auditory sensory epithelium
In: PLoS Genetics, Jg. 13 (2017-09-01), Heft 9
Online
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Zugriff:
The organ of Corti in the cochlea is a two-cell layered epithelium: one cell layer of mechanosensory hair cells that align into one row of inner and three rows of outer hair cells interdigitated with one cell layer of underlying supporting cells along the entire length of the cochlear spiral. These two types of epithelial cells are derived from common precursors in the four- to five-cell layered primordium and acquire functionally important shapes during terminal differentiation through the thinning process and convergent extension. Here, we have examined the role of Six1 in the establishment of the auditory sensory epithelium. Our data show that prior to terminal differentiation of the precursor cells, deletion of Six1 leads to formation of only a few hair cells and defective patterning of the sensory epithelium. Previous studies have suggested that downregulation of Sox2 expression in differentiating hair cells must occur after Atoh1 mRNA activation in order to allow Atoh1 protein accumulation due to antagonistic effects between Atoh1 and Sox2. Our analysis indicates that downregulation of Sox2 in the differentiating hair cells depends on Six1 activity. Furthermore, we found that Six1 is required for the maintenance of Fgf8 expression and dynamic distribution of N-cadherin and E-cadherin in the organ of Corti during differentiation. Together, our analyses uncover essential roles of Six1 in hair cell differentiation and formation of the organ of Corti in the mammalian cochlea.
Author summary Auditory sensory hair cells and surrounding supporting cells are derived from common prosensory progenitors, which undergo rearrangements through intercalation to achieve extension and establish the mosaic structure between hair and supporting cells. Hair cells are susceptible to damage from a variety of insults and are unable to regenerate. Through temporal deletion of Six1 in the developing cochlea, we found that Six1 activity is crucial for proper hair cell fate specification and for the regulation and maintenance of the spatiotemporal pattern of Sox2, Fgf8 and E- and N-cadherins during differentiation. Our data uncover novel roles of Six1 in hair cell differentiation during the formation of the organ of Corti.
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Six1 is essential for differentiation and patterning of the mammalian auditory sensory epithelium
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Autor/in / Beteiligte Person: | Maire, Pascal ; Xu, Jinshu ; Xu, Pin-Xian ; Zhang, Ting ; Bodescot, Myriam ; Department of Genetics and Genomic Sciences [New York, NY, États-Unis] ; Icahn School of Medicine at Mount Sinai [New York] (MSSM) ; Institut Cochin (IC UM3 (UMR 8104 / U1016)) ; Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) ; Developmental and Regenerative Biology [New York, NY, États-Unis] ; This research was funded by the NIH RO1DC014718 and New York STEM contract C029566 to PXX. |
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Zeitschrift: | PLoS Genetics, Jg. 13 (2017-09-01), Heft 9 |
Veröffentlichung: | Public Library of Science (PLoS), 2017 |
Medientyp: | unknown |
ISSN: | 1553-7404 (print) ; 1553-7390 (print) |
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