Radde-Gallwitz Kristen, Pan Ling, Gan Lin, Lin Xi, Segil Neil, Chen Ping
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
J Comp Neurol. 2004 Sep 27;477(4):412-21. doi: 10.1002/cne.20257.
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.
几个基本螺旋-环-螺旋（bHLH）基因已被证明对于听觉感觉毛细胞或支配耳蜗毛细胞的螺旋神经节（SG）神经元的产生至关重要，同时也对于其他神经系统中的多种细胞类型的产生至关重要。然而，尚不清楚何种细胞背景依赖机制赋予内耳特异性神经元或感觉能力/特性。我们探讨了一种可能性，即通过bHLH和LIM同源结构域（LIM-HD）转录因子的协同作用在神经系统中产生细胞多样性的机制之一，可能也有助于内耳特异性感觉和/或神经元能力的形成。在这里，我们表明，LIM-HD蛋白胰岛1（Isl1）在耳囊中早期表达于产生听觉感觉器官柯蒂氏器和SG神经元的区域。随后，Isl1的表达在SG神经元中得以维持，但在感觉谱系中是短暂的。在小鼠胚胎第12天（E12），Isl1的表达明显标记了新生耳蜗上皮包含原始柯蒂氏器的腹侧部分。在E13时，Isl1在感觉原基中维持在相对较高水平，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。Isl1在发育中的内耳中的表达揭示了内耳感觉和神经元谱系发育中的一个早期且可能是共同的步骤，并暗示了其在内耳特异性感觉和神经元细胞发育中的潜在作用。
