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

我们研究了典型神经干细胞标记物Musashi1在小鼠内耳中的表达模式。在年轻成年小鼠内耳，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。研究结果发表在Neuroscience letters(2004) 354, 201-204。我们的合作研究者之一冈野教授发现武藏1通过阻断Numb的功能激活Notch。Notch信号通路一直被认为在脊椎动物内耳发育中起着至关重要的作用。事实上，Notch相关基因的表达模式和jagged2缺陷小鼠的功能缺失实验结果表明，Notch信号通路的一个著名作用是侧向诱导，它在毛细胞和感觉上皮内支持细胞的精细马赛克模式的形成中起作用。因此，为了明确Musashi1在内耳发育和再生中的作用，我们认为有必要研究Notch激活在脊椎动物内耳中的时空表达模式。我们使用了一种特异性抗体来识别被早老素/ γ -分泌酶活性切割的Notch1细胞内结构域的加工形式。我们发现Notch1只在支持细胞谱系中被短暂激活，而在math1阳性毛细胞前体中根本没有发现Notch1的激活形式。这些结果发表在2005年ARO仲冬研究会议（2月19-24日，美国新奥尔良）上。

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.).