Differentiation of the lateral compartment of the cochlea requires a temporally restricted FGF20 signal.
Differentiation of the lateral compartment of the cochlea requires a temporally restricted FGF20 signal.
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DOI：
10.1371/journal.pbio.1001231
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发表时间：
2012-01
期刊：
影响因子：
9.8
通讯作者：
Ornitz DM
中科院分区：
文献类型：
--
作者：
Huh SH;Jones J;Warchol ME;Ornitz DM
小鼠中的FGF 20信号传导是耳蜗外毛细胞分化所必需的，耳蜗外毛细胞在年龄相关性听力损失期间最常受损。大部分与年龄相关的听力损失是由Corti器官中的外毛细胞损失或损伤引起的。Corti器官是内耳中的机械感觉转换装置，由内毛细胞、外毛细胞和高度特化的支持细胞组成。调节内毛细胞和外毛细胞分化的机制尚不清楚。在这里，我们报告说，成纤维细胞生长因子20（FGF20）是所需的分化细胞在耳蜗外侧区室（外毛和支持细胞）内的器官的Corti在特定的发展时间。在没有FGF20的情况下，小鼠是聋的，并且侧隔室细胞保持未分化、有丝分裂后和对Notch依赖性侧抑制无反应。这些研究确定了发育中不同的内侧（内毛和支持细胞）和外侧隔室在发展中的Corti器官。FGF20基因敲除小鼠的存活率和听力损失表明，FGF20也可能是人类的一个遗传相关基因。大部分与年龄相关的听力损失是由Corti器官中的外毛细胞损失或损伤引起的。Corti器官是内耳中的高度特化结构，由内毛细胞、外毛细胞和相关的支持细胞组成。虽然我们了解一些调节毛细胞与支持细胞分化的机制，但调节内毛细胞与外毛细胞分化的机制尚不清楚。一个潜在的候选者是成纤维细胞生长因子（FGF）信号传导，已知其调节许多感觉器官（包括Corti器官）的形态发生。在这项研究中，我们发现在发育过程中的特定时间需要FGF20信号传导来启动小鼠耳蜗外侧区室（包含外毛细胞和支持细胞，但不包含内毛细胞）中细胞的分化。在缺乏FGF20的情况下，小鼠是聋的，并且侧隔室细胞保持未分化并且对调节分化的最后阶段的机制无反应。考虑到外毛细胞在与年龄相关的听力损失中的重要性，这些发现具有重要意义。我们的研究还表明，FGF 20的基因突变可能导致人类耳聋，FGF 20可能是内耳感觉细胞修复或再生的重要因素。
FGF20 signaling in mice is required specifically for the differentiation of cochlear outer hair cells, the cells most often damaged during age-related hearing loss. A large proportion of age-related hearing loss is caused by loss or damage to outer hair cells in the organ of Corti. The organ of Corti is the mechanosensory transducing apparatus in the inner ear and is composed of inner hair cells, outer hair cells, and highly specialized supporting cells. The mechanisms that regulate differentiation of inner and outer hair cells are not known. Here we report that fibroblast growth factor 20 (FGF20) is required for differentiation of cells in the lateral cochlear compartment (outer hair and supporting cells) within the organ of Corti during a specific developmental time. In the absence of FGF20, mice are deaf and lateral compartment cells remain undifferentiated, postmitotic, and unresponsive to Notch-dependent lateral inhibition. These studies identify developmentally distinct medial (inner hair and supporting cells) and lateral compartments in the developing organ of Corti. The viability and hearing loss in Fgf20 knockout mice suggest that FGF20 may also be a deafness-associated gene in humans. A large proportion of age-related hearing loss is caused by loss or damage to outer hair cells in the organ of Corti. The organ of Corti is a highly specialized structure in the inner ear that is composed of inner hair cells, outer hair cells, and associated supporting cells. Although we understand some of the mechanisms that regulate hair cell versus supporting cell differentiation, the mechanisms that regulate differentiation of inner versus outer hair cells are not known. One potential candidate is fibroblast growth factor (FGF) signaling, which is known to regulate the morphogenesis of many sensory organs, including the organ of Corti. In this study, we find that FGF20 signaling is required at a specific time during development to initiate differentiation of cells in the mouse lateral cochlear compartment (which contains outer hair cells and supporting cells, but not inner hair cells). In the absence of FGF20, mice are deaf, and lateral compartment cells remain undifferentiated and unresponsive to mechanisms that regulate the final stages of differentiation. These findings are significant given the importance of outer hair cells during age-related hearing loss. Our studies also suggest that genetic mutations in FGF20 may result in deafness in humans and that FGF20 may be an important factor for the repair or regeneration of sensory cells in the inner ear.
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影响因子：
2.5
作者：
Hayashi, Toshinori;Ray, Catherine A.;Younkins, Christa;Bermingham-McDonogh, Olivia
通讯作者：
Bermingham-McDonogh, Olivia
DOI：
10.1083/jcb.137.6.1287
发表时间：
1997-06-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hasson T;Gillespie PG;Garcia JA;MacDonald RB;Zhao Y;Yee AG;Mooseker MS;Corey DP
通讯作者：
Corey DP
影响因子：
16.2
作者：
Pirvola, U;Ylikoski, J;Partanen, J
通讯作者：
Partanen, J
影响因子：
2.5
作者：
Kim, Euysoo;Hyrc, Krzysztof L.;Ornitz, David M.
通讯作者：
Ornitz, David M.
DOI：
10.1097/moo.0b013e3283303347
发表时间：
2009-10
影响因子：
1.6
作者：
Kelley MW;Driver EC;Puligilla C
通讯作者：
Puligilla C