The investigation of the roles of Notch signaling pathway during the mammalian inner ear development and its application to the to the hair cell regeneration

Notch信号通路在哺乳动物内耳发育过程中的作用及其在毛细胞再生中的应用研究

• 批准号: 18591866
• 负责人: MURATA Junko
• 金额: $ 2.35万
• 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: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591866/
• 关键词: Development of inner ear; Notch signaling pathway; Hair cell; Supporting cell; Cell differentiation; Prosensory region; Notch-Hes1経路; 蝸牛; p27Kip1; Math1; BrdU陽性細胞; Notch伝達系; 感覚上皮前駆細胞; Hes1; p27^<Kip1>; 増殖維持

The Notch signaling pathway has been thought to play a crucial role in the development of mammalian inner ear. Supported by the Grant-in-Aid for Scientific Research <KAKENHI> #18591866, we investigated the spatio-temporal activation pattern of Notchl using the antibody that specifically recognizes the activated form of Notchl (actN1) to clarify the multiple roles of the Notch pathway during the inner ear development. Between embryonic days (E) 12.5 and E14.5, actN1 was weakly detected mainly in the medial region of the cochlear epithelium, where Jagged1 (Jag1)-immunoreactivity (IR) was also observed. Jag1-IR gradually became stronger in a more sharply defined area, finally becoming localized in supporting cells, while actN1 was detected in an overlapping area Thus, a positive feed-back loop was assumed to exit between the expression of Jag1 and actN1. In addition, actN1 started to be strongly expressed in the cells surrounding Mathl-positive hair cell progenitors between E14.5 and E15.5. Strong actN1-IR continued in both a supporting cell linege and in the greater epithelial ridge during the perinatal stage but ended by P7, suggesting that Notchl activation may initially demarcate a prosensory region in the cochlear epithelium and then inhibit progenitor cells from becoming hair cells via classical "lateral inhibition."

Notch信号通路被认为在哺乳动物内耳的发展中起着至关重要的作用。在科学研究的赠款中，我们使用抗体研究了NotCHL的时空激活模式，该抗体使用抗体进行了时空激活模式，该抗体专门识别Notchl的激活形式（ACTN1），以阐明内耳朵发育过程中Notch途径的多重作用。在胚胎天（E）12.5和E14.5之间，ACTN1主要检测到在耳蜗上皮的内侧区域，在那里也观察到jagged1（jag1） - 免疫反应性（IR）。 Jag1-ir在更明确的区域逐渐变得更强大，最终在支撑细胞中局部，而在重叠区域中检测到ACTN1，因此假定阳性馈回回路在JAG1和ACTN1的表达之间退出。此外，ACTN1在E14.5和E15.5之间的数学阳性毛细胞祖细胞周围的细胞中开始强烈表达。强大的ACTN1-IR在围产期阶段的支持细胞线路和更大的上皮脊中继续进行，但以P7结束，这表明Notchl激活最初可能会划分人工耳蜗上皮中的一个处相区域，然后通过经典的“以后抑制作用”抑制毛细胞。”

项目成果

Hes1 Contributes the Proliferative Capacity of Sensory Precursors in Addition to the Cell Diversification during Mammalian Inner Ear Development.

在哺乳动物内耳发育过程中，Hes1 除了促进细胞多样化外，还有助于感觉前体的增殖能力。

• 发表时间: 2007
• 作者: Murata J;Tokunaga A;Ohtsuka T;Kageyama R;Doi K;Horii A;Tamura M;Iwaki T;Kubo T;Okano H
• 通讯作者: Okano H

The roles of Notch-Hesl pathway in the formation of prosensory region during mammalian cochlear development.

Notch-Hesl 通路在哺乳动物耳蜗发育过程中前感觉区形成中的作用。

• 发表时间: 2008
• 期刊: The Abstracts of the 31thARO MWM Vol.31
• 作者: Murata J;Ohtsuka T;Tokunaga A;Okano H;Kageyama R;et. al.
• 通讯作者: et. al.

The Roles of Notch-Hes1 Pathway in the Formation of Prosensory Region during Mammalian Cochlear Development.

Notch-Hes1 通路在哺乳动物耳蜗发育过程中前感觉区形成中的作用。

• 发表时间: 2008
• 作者: Murata J;Ohtsuka T;Tokunaga A;Tamura M;Horii A;Doi K;Kageyama R;Okano H
• 通讯作者: Okano H

Notch伝達系による内耳感覚上皮前駆細胞の増殖制御について

Notch转导系统控制内耳感觉上皮祖细胞的增殖

• 发表时间: 2006
• 作者: 村田潤子;土井勝美;堀井新;識名崇;川島貴之;森鼻哲生;端山昌樹;岡野栄之;久保武
• 通讯作者: 久保武

The regulation of the proliferative capacity of auditory sensory precursor cells by the Notch signaling pathway.

Notch 信号通路对听觉感觉前体细胞增殖能力的调节。

• 发表时间: 2006
• 作者: Murata J;Doi K;Horii A;Shikina T;Kawashima T;Morihana T;Hayama M;Okano H;Kubo T
• 通讯作者: Kubo T