Sox2 induces neuronal formation in the developing mammalian cochlea.
Sox2 induces neuronal formation in the developing mammalian cochlea.
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DOI：
10.1523/jneurosci.3852-09.2010
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发表时间：
2010-01-13
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影响因子：
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通讯作者：
Kelley MW
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文献类型：
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作者：
Puligilla C;Dabdoub A;Brenowitz SD;Kelley MW
在耳蜗中，螺旋神经节神经元在听力中起着至关重要的作用，因为它们在内耳的机械感觉毛细胞和脑干的耳蜗核之间形成了中继站。神经性碱性螺旋-环-螺旋(BHLH)转录因子Neurogenin1(Neurog1)和NeuroD1对于耳囊来源的内耳感觉神经元的发育是必不可少的。在这里，我们展示了耳蜗非感觉上皮细胞的神经功能，因为Neurog1或Neurod1的异位表达导致神经细胞的形成。由于高迁移率族(HMG)转录因子Sox2在耳囊来源的神经前体细胞中表达，随后与Neurog1和NeuroD1一起在螺旋神经节神经元中表达，我们利用获得和功能丧失实验来研究Sox2在螺旋神经节神经元形成中的作用。我们证明了Sox2的过度表达导致了神经元的产生，这表明Sox2足以诱导无感觉上皮细胞的神经元命运。此外，Sox2Lcc/LCC小鼠耳蜗中没有螺旋神经节神经元，这表明Sox2也是耳蜗神经元形成所必需的。我们的结果表明，Sox2、Neurog1和NeuroD1足以诱导耳蜗非感觉区的神经元命运。最后，我们证明了耳蜗内的非感觉细胞至少在出生后早期都保持着神经能力。
In the cochlea, spiral ganglion neurons play a critical role in hearing as they form the relay between mechanosensory hair cells in the inner ear and cochlear nuclei in the brainstem. The proneural basic helix-loop-helix (bHLH) transcription factors Neurogenin1 (Neurog1) and NeuroD1 have been shown to be essential for the development of otocyst-derived inner ear sensory neurons. Here we show neural competence of non-sensory epithelial cells in the cochlea as ectopic expression of either Neurog1 or NeuroD1 results in the formation of neuronal cells. Since the high-mobility-group type (HMG) transcription factor Sox2, which is also known to play a role in neurogenesis, is expressed in otocyst-derived neural precursor cells and later in the spiral ganglion neurons along with Neurog1 and NeuroD1, we utilized both gain- and loss-of-function experiments to examine the role of Sox2 in spiral ganglion neuron formation. We demonstrate that overexpression of Sox2 results in the production of neurons, suggesting that Sox2 is sufficient for the induction of neuronal fate in non-sensory epithelial cells. Furthermore, spiral ganglion neurons are absent in cochleae from Sox2Lcc/Lcc mice, indicating that Sox2 is also required for neuronal formation in the cochlea. Our results indicate that Sox2, along with Neurog1 and NeuroD1, are sufficient to induce a neuronal fate in non-sensory regions of the cochlea. Finally, we demonstrate that non-sensory cells within the cochlea retain neural competence through at least the early postnatal period.