Fine-tuning of Notch signaling sets the boundary of the organ of Corti and establishes sensory cell fates.
Fine-tuning of Notch signaling sets the boundary of the organ of Corti and establishes sensory cell fates.
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DOI：
10.7554/elife.19921
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发表时间：
2016-12-14
期刊：
影响因子：
7.7
通讯作者：
Groves AK
中科院分区：
文献类型：
--
作者：
Basch ML;Brown RM 2nd;Jen HI;Semerci F;Depreux F;Edlund RK;Zhang H;Norton CR;Gridley T;Cole SE;Doetzlhofer A;Maletic-Savatic M;Segil N;Groves AK
诱导Corti器官并定义其在耳蜗中的边界的信号知之甚少。我们发现，两个Notch修饰符，Lfng和Mfng，是瞬时精确表达的神经边界的器官的Corti。Cre-Lox基因定位显示该区域产生内毛细胞及其相关的内趾骨细胞。Lfng和Mfng的突变破坏了这一边界，产生了意想不到的内毛细胞和内指骨细胞的复制。这种表型被其他小鼠突变体或降低但不消除Notch信号传导的药物治疗所模仿。然而，Notch信号的强烈破坏导致了一个非常不同的结果，以牺牲内指骨细胞为代价产生了许多异位毛细胞。我们的研究结果表明，Notch信号在耳蜗中被精细校准，以产生精确调谐的信号水平，该信号水平首先设定Corti器官的边界，然后调节毛细胞发育。DOI：http://dx.doi.org/10.7554/eLife.19921.001网站
The signals that induce the organ of Corti and define its boundaries in the cochlea are poorly understood. We show that two Notch modifiers, Lfng and Mfng, are transiently expressed precisely at the neural boundary of the organ of Corti. Cre-Lox fate mapping shows this region gives rise to inner hair cells and their associated inner phalangeal cells. Mutation of Lfng and Mfng disrupts this boundary, producing unexpected duplications of inner hair cells and inner phalangeal cells. This phenotype is mimicked by other mouse mutants or pharmacological treatments that lower but not abolish Notch signaling. However, strong disruption of Notch signaling causes a very different result, generating many ectopic hair cells at the expense of inner phalangeal cells. Our results show that Notch signaling is finely calibrated in the cochlea to produce precisely tuned levels of signaling that first set the boundary of the organ of Corti and later regulate hair cell development. DOI: http://dx.doi.org/10.7554/eLife.19921.001