The role of Musashi1in the development and regeneration of vertebrate Inner ear

Musashi1在脊椎动物内耳发育和再生中的作用

基本信息

批准号：
15591814
负责人：
MURATA Junko
金额：
$ 2.3万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591814/
关键词：
Musashi1 sensory epithelium of inner ear regeneration Notch signaling pathway hair cell supporting cell Math1 activated Notch1 Hes1

项目摘要

We have been investigated the expression pattern of Musashi1, one of typical neural stem cell markers in mouse inner ear. In the inner ear of young adult mice, Musashi1 immuno-positive cells were observed in vestibular and cochlear ganglion cells and supporting cells within the sensonsory epithelium. The results were published in Neuroscience letters 354 (2004), 201-204. Prof.Okano, one of our co-investigators, showed that Musashi1 activates Notch through blocking the function of Numb. Notch signaling pathway has been thought to play a crucial role in vertebrate inner ear development. Indeed, the expression pattern of Notch-related genes and the result of function-loss experiments using Jagged2-deficient mice, indicated that lateral induction, one of famous role of Notch signaling pathway, functions in the formation of a fine mosaic pattern of hair cells and supporting cells in the sensory epithelium. Thus to clarify the role of Musashi1 in the development and regeneration of inner ear, we thought that it is important to investigate the spatio-temporal expression pattern of Notch activation in vertebrate inner ear. We used a specific antibody that recognizes the processed form of the intracellular domain of Notch1 cleaved by presenilin/gamma-secretase activity. We indicated that Notch1 was transiently activated exclusively in supporting cell lineage and the activated form of Notch1 was not found at all in math1 positive hair cell precursors. These results were presented at 2005 ARO Midwinter Research Meeting (February 19-24, New Orleans, U.S.A.).

我们研究了小鼠内耳中典型神经干细胞标记物之一Musashi1的表达模式。在年轻成年小鼠的内耳中，在前庭和耳蜗神经节细胞以及感觉上皮内的支持细胞中观察到 Musashi1 免疫阳性细胞。结果发表在 Neuroscience letter 354 (2004), 201-204 上。我们的合作研究员之一 Okano 教授表明 Musashi1 通过阻断 Numb 的功能来激活 Notch。 Notch信号通路被认为在脊椎动物内耳发育中发挥着至关重要的作用。事实上，Notch 相关基因的表达模式和使用 Jagged2 缺陷小鼠进行的功能丧失实验结果表明，横向诱导（Notch 信号通路的著名作用之一）在毛细胞精细镶嵌图案的形成中发挥作用。和感觉上皮中的支持细胞。因此，为了阐明Musashi1在内耳发育和再生中的作用，我们认为研究脊椎动物内耳中Notch激活的时空表达模式非常重要。我们使用了一种特异性抗体，可以识别由早老素/γ分泌酶活性切割的 Notch1 胞内结构域的加工形式。我们指出，Notch1 仅在支持细胞谱系中短暂激活，并且在 math1 阳性毛细胞前体中根本没有发现 Notch1 的激活形式。这些结果在 2005 年 ARO 仲冬研究会议（2 月 19 日至 24 日，美国新奥尔良）上公布。