Expression of Islet1 marks the sensory and neuronal lineages in the mammalian inner ear

Expression of Islet1 marks the sensory and neuronal lineages in the mammalian inner ear
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DOI:
10.1002/cne.20257
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发表时间:
2004-09-27
影响因子:
2.5
通讯作者:
Chen, P
Chen, P
中科院分区:
医学3区
文献类型:
--
作者:
Radde-Gallwitz, K;Pan, L;Chen, P

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几个基本的螺旋-环-螺旋(bHLH)基因已被证明对于听觉毛细胞或支配耳蜗中毛细胞的螺旋神经节(SG)神经元以及其他神经系统中的多种细胞类型的产生是必需的。然而,它仍然是难以捉摸的细胞环境依赖性机制赋予内耳特异性神经元或感觉能力/身份。我们探讨的可能性,负责产生细胞多样性的神经系统通过合作行动的bHLH和LIM同源结构域(LIM-HD)转录因子的机制之一,也可能有助于内耳特异性的感觉和/或神经元的能力。在这里,我们表明,Islet 1(Isl 1),LIM-HD蛋白,在该地区的耳囊早期表达,引起听觉感觉器官,Corti器官,和SG神经元。随后,Isl 1的表达维持在SG神经元中,但在感觉谱系中是暂时的。在小鼠胚胎第12天(E12),Isl 1的表达明显标志着新生耳蜗上皮的腹侧部分,包括原始的Corti器官。在E13,Isl 1在感觉原基中维持在相对高的水平,而在耳蜗管的其他区域下调。随着感觉上皮开始分化,它在整个耳蜗上皮中下调。Isl 1在发育中的内耳中的表达揭示了内耳感觉和神经谱系发育中的早期和可能的共同步骤,并表明其在内耳特异性感觉和神经细胞发育中的潜在作用。
Several basic helix-loop-helix (bHLH) genes have been shown to be essential for the generation of the auditory sensory hair cells or the spiral ganglion (SG) neurons that innervate the hair cells in the cochlea, as well as a variety of cell types in the other nervous systems. However, it remains elusive what cellular context-dependent mechanisms confer the inner ear-specific neuronal or sensory competency/identities. We explored the possibility that one of the mechanisms responsible for generating cellular diversity in the nervous system through cooperative action of bHLH and LIM-homeodomain (LIM-HD) transcriptional factors might also contribute to the inner ear-specific sensory and/or neuronal competency. Here, we show that Islet1 (Isl1), a LIM-HD protein, is expressed early in the otocyst in the region that gives rise to both the auditory sensory organ, the organ of Corti, and SG neurons. Subsequently, the expression of Isl1 is maintained in SG neurons but is transitory in the sensory lineage. At embryonic day 12 (E12) in mice, the expression of Isl1 marks distinctively the ventral portion of the nascent cochlear epithelium encompassing the primordial organ of Corti. At E13, Isl1 is maintained at relatively high levels in the sensory primordium while down-regulated in the other regions of the cochlear duct. As the sensory epithelium starts to differentiate, it is down-regulated in the entire cochlear epithelium. The expression of Isl1 in the developing inner ear reveals an early and likely a common step in the development of both sensory and neuronal lineages of the inner ear, and suggests its potential role in the inner ear-specific sensory and neuronal cell development.