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

我们研究了神经干细胞标志物Musashi 1在小鼠内耳中的表达模式。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Musashi 1免疫阳性细胞。研究结果发表在Neuroscience Letters 354（2004），201-204。我们的合作研究者之一冈野教授表明，武藏1通过阻断麻木的功能来激活Notch。Notch信号通路被认为在脊椎动物内耳发育中起着至关重要的作用。事实上，Notch相关基因的表达模式和使用Jagged 2缺陷小鼠的功能丧失实验的结果表明，Notch信号通路的著名作用之一的侧向诱导在感觉上皮中毛细胞和支持细胞的精细镶嵌模式的形成中起作用。因此，研究Notch在脊椎动物内耳中的时空表达模式对阐明Musashi 1在内耳发育和再生中的作用具有重要意义。我们使用了一种特异性抗体，该抗体识别由早老素/γ-分泌酶活性切割的Notch 1细胞内结构域的加工形式。我们发现Notch 1仅在支持细胞系中被瞬时激活，而在math 1阳性毛细胞前体中根本没有发现Notch 1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。

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.).