Artificial induction of Sox21 regulates sensory cell formation in the embryonic chicken inner ear.
Artificial induction of Sox21 regulates sensory cell formation in the embryonic chicken inner ear.
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DOI：
10.1371/journal.pone.0046387
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Daudet N
中科院分区：
文献类型：
--
作者：
Freeman SD;Daudet N
在胚胎发育过程中，内耳感觉上皮中的毛细胞和支持细胞来源于表达Sox2的祖细胞，Sox2是转录因子SoxB1家族的成员。Sox 2是必不可少的感觉规范，但高水平的Sox 2表达似乎抑制毛细胞分化，这表明调节Sox 2活性的因素可能是至关重要的两个过程。已知SoxB1和SoxB2因子之间的拮抗相互作用调节神经组织中的细胞分化，这使我们研究了SoxB2成员Sox21在鸡内耳发育过程中的潜在作用。Sox 21通常由早期胚胎鸡内耳前庭和听觉区域内的感觉祖细胞表达。在后期阶段，Sox 21在前庭和听觉器官中差异表达。Sox 21仅限于听觉上皮的支持细胞层，而在前庭器官的毛细胞层中富集。为了测试Sox21函数，我们使用了两种时间上不同的函数增益方法。持续过度表达的Sox 21从早期发育阶段阻止prosensory规范，并取消了毛细胞和支持细胞的形成。然而，在前庭上皮的器官型培养物中，在毛细胞形成时诱导Sox 21表达抑制了内源性Sox 2表达和Notch活性，并使祖细胞偏向毛细胞命运。有趣的是，Sox 21并没有促进毛细胞分化的未成熟的听觉上皮，这符合内源性Sox 21的表达在成熟的支持细胞在这个组织。这些结果表明，内源性SoxB家族转录因子之间的相互作用可能会调节内耳感觉细胞的形成，但在上下文依赖的方式。
During embryonic development, hair cells and support cells in the sensory epithelia of the inner ear derive from progenitors that express Sox2, a member of the SoxB1 family of transcription factors. Sox2 is essential for sensory specification, but high levels of Sox2 expression appear to inhibit hair cell differentiation, suggesting that factors regulating Sox2 activity could be critical for both processes. Antagonistic interactions between SoxB1 and SoxB2 factors are known to regulate cell differentiation in neural tissue, which led us to investigate the potential roles of the SoxB2 member Sox21 during chicken inner ear development. Sox21 is normally expressed by sensory progenitors within vestibular and auditory regions of the early embryonic chicken inner ear. At later stages, Sox21 is differentially expressed in the vestibular and auditory organs. Sox21 is restricted to the support cell layer of the auditory epithelium, while it is enriched in the hair cell layer of the vestibular organs. To test Sox21 function, we used two temporally distinct gain-of-function approaches. Sustained over-expression of Sox21 from early developmental stages prevented prosensory specification, and abolished the formation of both hair cells and support cells. However, later induction of Sox21 expression at the time of hair cell formation in organotypic cultures of vestibular epithelia inhibited endogenous Sox2 expression and Notch activity, and biased progenitor cells towards a hair cell fate. Interestingly, Sox21 did not promote hair cell differentiation in the immature auditory epithelium, which fits with the expression of endogenous Sox21 within mature support cells in this tissue. These results suggest that interactions among endogenous SoxB family transcription factors may regulate sensory cell formation in the inner ear, but in a context-dependent manner.
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影响因子：
5.7
作者：
Edge AS;Chen ZY
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DOI：
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发表时间：
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