Sox2 is required for sensory organ development in the mammalian inner ear
Sox2 is required for sensory organ development in the mammalian inner ear
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DOI：
10.1038/nature03487
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发表时间：
2005-04-21
期刊：
影响因子：
64.8
通讯作者：
Cheah, KSE
中科院分区：
文献类型：
--
作者：
Kiernan, AE;Pelling, AL;Cheah, KSE
内耳中的感觉毛细胞及其相关的非感觉支持细胞是听力和平衡的基础。它们起源于一个共同的祖细胞(1)，但人们对指定该细胞谱系的分子事件知之甚少。我们最近发现了两个小鼠的等位基因突变体，Lcc和YSb，它们表现出听力和平衡障碍。LCC/LCC小鼠是完全失聪的，而YSB/YSB小鼠是严重听力受损的(2)。本文报道LCC/LCC小鼠内耳不能建立前感觉域，毛细胞和支持细胞均不分化，导致严重的内耳畸形，而YSB/YSB小鼠感觉上皮发育异常，毛细胞排列紊乱，数量减少。这些表型是由于转录因子SOX2缺乏(在lcc突变体中)或表达减少(在ysb突变体中)，特别是在发育中的内耳中。Sox2在缺少Math1(也称为Atoh1和HATH1)的小鼠内耳中继续表达，而Math1在LCC突变体中不表达，这表明Sox2作用于Math1的上游。
Sensory hair cells and their associated non-sensory supporting cells in the inner ear are fundamental for hearing and balance. They arise from a common progenitor(1), but little is known about the molecular events specifying this cell lineage. We recently identified two allelic mouse mutants, light coat and circling (Lcc) and yellow submarine (Ysb), that show hearing and balance impairment(2). Lcc/Lcc mice are completely deaf, whereas Ysb/Ysb mice are severely hearing impaired(2). We report here that inner ears of Lcc/Lcc mice fail to establish a prosensory domain and neither hair cells nor supporting cells differentiate, resulting in a severe inner ear malformation, whereas the sensory epithelium of Ysb/Ysb mice shows abnormal development with disorganized and fewer hair cells. These phenotypes are due to the absence (in Lcc mutants) or reduced expression (in Ysb mutants) of the transcription factor SOX2, specifically within the developing inner ear. SOX2 continues to be expressed in the inner ears of mice lacking Math1 (also known as Atoh1 and HATH1), a gene essential for hair cell differentiation, whereas Math1 expression is absent in Lcc mutants, suggesting that Sox2 acts upstream of Math1.