Canonical Notch signaling is not necessary for prosensory induction in the mouse cochlea: insights from a conditional mutant of RBPjkappa.
Canonical Notch signaling is not necessary for prosensory induction in the mouse cochlea: insights from a conditional mutant of RBPjkappa.
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DOI：
10.1523/jneurosci.6671-10.2011
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发表时间：
2011-06-01
期刊：
影响因子：
--
通讯作者：
Groves AK
中科院分区：
文献类型：
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作者：
Basch ML;Ohyama T;Segil N;Groves AK
哺乳动物的Corti器官由一系列高度组织化的毛细胞和支持细胞组成，这些细胞来源于共同的前感觉祖细胞群体。这种复杂的细胞嵌合体的正确分化需要由Notch信号传导介导的侧向抑制。几项研究还表明，Notch信号传导参与了前感觉域的早期诱导，前感觉域位于沿着耳蜗导管的长度，并且在毛细胞和支持细胞分化开始之前形成。为了研究Notch信号传导在前感觉域形成中的作用，我们在整个内耳中条件性地失活经典Notch信号传导的转录介质RBPjκ。虽然RBPjκ突变体具有严重的前庭缺陷和缩短的耳蜗管，但在RBPjκ突变体的耳蜗中，前感觉域的标记物出现在正常的时间和位置。尽管没有RBPjκ，但耳蜗毛细胞和支持细胞标记物也在适当的时间出现，表明RBPjκ在耳蜗感觉上皮的分化中起重要作用。然而，我们也观察到，分化中的毛细胞和支持细胞在RBPjκ突变体中迅速死亡，这表明RBPjκ对该组织中细胞存活的要求。最后，与鸡基底乳头相反，Notch信号的异位激活在耳蜗的非感觉区域中不诱导异位感觉贴片。我们的研究结果表明，典型的Notch信号是不必要的prosensory规格在小鼠耳蜗，这表明其他信号通路可能指定这个高度衍生的感觉器官。
The mammalian organ of Corti consists of a highly organized array of hair cells and supporting cells that originate from a common population of prosensory progenitors. Proper differentiation of this complex cellular mosaic requires lateral inhibition mediated by Notch signaling. Several studies also have implicated Notch signaling in the earlier induction of the prosensory domain that lies along the length of the cochlear duct, and which forms prior to the onset of hair cell and supporting cell differentiation. To investigate the role of Notch signaling in prosensory domain formation, we conditionally inactivated the transcriptional mediator of canonical Notch signaling, RBPjκ, throughout the inner ear. While RBPjκ mutants have severe vestibular defects and a shortened cochlear duct, markers of the prosensory domain appear at the normal time and location in the cochlea of RBPjκ mutants. Despite the lack of RBPjκ, hair cell and supporting cell markers also appear at appropriate times in the cochlea, suggesting that RBPjκ is dispensable for differentiation of the cochlear sensory epithelium. However, we also observed that differentiating hair cells and supporting cells rapidly die in RBPjκ mutants, suggesting a requirement of RBPjκ for cell survival in this tissue. Finally, in contrast to the chick basilar papilla, ectopic activation of Notch signaling did not induce ectopic sensory patches in non-sensory regions of the cochlea. Our results indicate that canonical Notch signaling is not necessary for prosensory specification in the mouse cochlea, suggesting that other signaling pathways may specify this highly derived sensory organ.