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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Notch signaling specifies prosensory domains via lateral induction in the developing mammalian inner ear
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Notch signaling specifies prosensory domains via lateral induction in the developing mammalian inner ear

机译：Notch信号传导通过发育中的哺乳动物内耳中的侧向感应来指定前感觉域

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摘要

During inner ear morphogenesis, the process of prosensory specification defines the specific regions of the otic epithelium that will give rise to the six separate inner ear organs essential for hearing and balance. The mechanism of prosensory specification is not fully understood, but there is evidence that the Notch intercellular signaling pathway plays a critical role. The Notch ligand Jagged 1 (Jag1) is expressed in the prosensory domains, and mutation of Jag1 impairs sensory formation. Furthermore, pharmacological inhibition of Notch in vitro during prosensory specification disrupts the prosensory process. Additionally, activation of Notch by cDNA electroporation in chick otocysts results in formation of ectopic sensory patches. Here we test whether Notch activity is sufficient for prosensory specification in the mouse, using a Cre-/IoxP approach to conditionally activate the Notch pathway in nonsensory regions of the inner ear epithelia during different stages of otic vesicle morphogenesis. We find that broad ectopic activation of Notch at very early developmental stages causes induction of prosensory markers throughout the entire otic epithelium. At later stages of development, activation of Notch in nonsensory regions leads to induction of sensory patches that later differentiate to form complete ectopic sensory structures. Activation of Notch in isolated nonsensory cells results in lateral induction of Jag1 expression in neighboring cells and spreading of prosensory specification to the adjacent cells through an intercellular mechanism. These results support a model where activation of Notch and propagation through lateral induction promote prosensory character in specific regions of the developing otocyst.
机译：在内耳形态发生过程中，感觉规范的过程定义了耳上皮的特定区域，这些区域会产生六个独立的内耳器官，这对听力和平衡至关重要。感觉规范的机制尚不完全清楚，但有证据表明，Notch细胞间信号通路起着关键作用。 Notch配体锯齿状1（Jag1）在前感觉域中表达，并且Jag1的突变会损害感觉形成。此外，在感觉规范期间体外Notch的药理学抑制作用破坏了感觉过程。另外，通过在鸡卵囊中进行cDNA电穿孔激活Notch会导致异位感觉斑的形成。在这里，我们通过使用Cre- / IoxP方法在耳泡囊泡形态发生的不同阶段有条件地激活内耳上皮非感觉区域的Notch通路，来测试Notch活性是否足以满足小鼠的感觉规范要求。我们发现Notch的广泛异位激活在非常早期的发展阶段会导致整个耳上皮中的感觉标记的诱导。在发育的后期，Notch在非感觉区域的激活会导致感觉斑块的诱导，随后分化形成完整的异位感觉结构。 Notch在分离的非感觉细胞中的激活导致Jag1在邻近细胞中的横向诱导，并通过细胞间机制将前感觉指标扩散到邻近细胞。这些结果支持了一个模型，在该模型中，Notch的激活和通过侧向诱导的传播促进了发育中的耳囊特定区域的感觉特性。

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    Byron H. Hartman; Thomas A. Reh; Olivia Bermingham-McDonogh;

  • 作者单位

    Department of Biological Structure, University of Washington, Seattle, WA 98195 lnstitute for Stem Cells and Regenerative Medicine, University of Washington, Seattle, WA 98109;

    rnDepartment of Biological Structure, University of Washington, Seattle, WA 98195 lnstitute for Stem Cells and Regenerative Medicine, University of Washington, Seattle, WA 98109;

    rnDepartment of Biological Structure, University of Washington, Seattle, WA 98195 lnstitute for Stem Cells and Regenerative Medicine, University of Washington, Seattle, WA 98109 Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, WA 98195;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    jagged 1; lateral inhibition; otic development; sensory epithelium; sensory induction;

    机译：锯齿状的1;横向抑制耳部发育感觉上皮感官诱导;

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