Six1 is essential for differentiation and patterning of the mammalian auditory sensory epithelium.
Six1 is essential for differentiation and patterning of the mammalian auditory sensory epithelium.
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DOI：
10.1371/journal.pgen.1006967
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发表时间：
2017-09
期刊：
影响因子：
4.5
通讯作者：
Xu PX
中科院分区：
文献类型：
--
作者：
Zhang T;Xu J;Maire P;Xu PX
耳蜗中的Corti器是两细胞分层上皮：一层机械感觉毛细胞排列成一排内毛细胞和三排外毛细胞，与一层下层支持细胞沿耳蜗螺旋的整个长度沿着交错。这两种类型的上皮细胞来源于4 - 5细胞层状原基中的共同前体，并在终末分化过程中通过变薄过程和会聚延伸获得功能重要的形状。在这里，我们已经研究了Six 1在听觉感觉上皮的建立中的作用。我们的数据表明，在前体细胞的终末分化之前，Six 1的缺失导致仅形成少数毛细胞和感觉上皮的缺陷图案。以前的研究表明，下调分化毛细胞中的Sox 2表达必须发生在Atoh 1 mRNA激活后，以允许Atoh 1蛋白的积累，由于Atoh 1和Sox 2之间的拮抗作用。我们的分析表明，Sox 2在分化的毛细胞中的下调依赖于Six 1活性。此外，我们发现Six 1是维持分化过程中Corti器中Fgf 8表达和N-cadherin和E-cadherin动态分布所必需的。总之，我们的分析揭示了Six 1在哺乳动物耳蜗毛细胞分化和Corti器官形成中的重要作用。听觉感觉毛细胞和周围的支持细胞来源于共同的前感觉祖细胞，其通过嵌入进行重排以实现延伸并在毛和支持细胞之间建立镶嵌结构。毛细胞容易受到各种损伤的损害，并且无法再生。通过在发育中的耳蜗中暂时缺失Six 1，我们发现Six 1活性对于正确的毛细胞命运规范以及在分化过程中调节和维持Sox 2，Fgf 8和E-和N-钙粘蛋白的时空模式至关重要。我们的数据揭示了Six 1在Corti器形成过程中毛细胞分化中的新作用。
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. 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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影响因子：
11.8
作者：
Ahmed, Mohi;Wong, Elaine Y. M.;Sun, Jianbo;Xu, Jinshu;Wang, Feng;Xu, Pin-Xian
通讯作者：
Xu, Pin-Xian
DOI：
10.1073/pnas.0808175105
发表时间：
2008-11-25
影响因子：
11.1
作者：
Dabdoub, Alain;Puligilla, Chandrakala;Kelley, Matthew W.
通讯作者：
Kelley, Matthew W.
影响因子：
4.6
作者：
Grifone, R;Demignon, J;Maire, P
通讯作者：
Maire, P
影响因子：
9.8
作者：
Hoskins, Bethan E.;Cramer, Carl H., II;Hildebrandt, Friedhelm
通讯作者：
Hildebrandt, Friedhelm
影响因子：
3.6
作者：
KONIG, R;FUCHS, S;DUKIET, C
通讯作者：
DUKIET, C