Deficiency of large tumor suppressor kinase 1 causes congenital hearing loss associated with cochlear abnormalities in mice
Deficiency of large tumor suppressor kinase 1 causes congenital hearing loss associated with cochlear abnormalities in mice
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DOI：
10.1016/j.bbrc.2020.10.073
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发表时间：
2021-01-01
影响因子：
3.1
通讯作者：
Ogawa, Kaoru
中科院分区：
文献类型：
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作者：
Nishiyama, Takanori;Fujioka, Masato;Ogawa, Kaoru
哺乳动物的听毛细胞不会自发地被替换。它们的数量和协调的极化保持得相当好，这两个因素对耳蜗放大器来说都是必不可少的。细胞周期调节在调节适当的细胞大小和细胞数量中具有关键作用。然而，对Hippo通路的生理作用知之甚少，Hippo通路是调节耳蜗感觉上皮细胞生长、分化和再生能力的最重要的信号级联之一。在此，我们研究了大肿瘤抑制因子1（LATS 1），在海马/yes相关蛋白通路中的一种必需激酶，在耳蜗中使用LATS 1敲除小鼠的体内作用。LATS 1在毛细胞和支持细胞中表达。在Corti器的表皮板表面有强表达。我们发现LATS 1基因敲除导致先天性听力损失，这是由于毛细胞的方向不规则和数量略有减少，而支持细胞的数量保持不变。在毛细胞表面，动纤毛和静纤毛在形态发生期间和之后分散。然而，受体非依赖性极性调节因子（例如Par 3或Gai）的表达不受影响。我们的结论是LATS 1在哺乳动物听毛细胞的成熟过程中起着不可或缺的作用，但在支持细胞的发育过程中不起作用，因此，LATS 1在听觉获得中起作用。(c)2020爱思唯尔公司All rights reserved.
Mammalian auditory hair cells are not spontaneously replaced. Their number and coordinated polarization are fairly well-maintained and both these factors might be essential for the cochlear amplifier. Cell cycle regulation has critical roles in regulating appropriate cell size and cell number. However, little is known about the physiological roles of the Hippo pathway, which is one of the most important signaling cascades that regulates cell growth, differentiation, and regenerative capacity in the cochlear sensory epithelium. Herein, we investigated the in vivo role of the large tumor suppressor 1 (LATS1), an essential kinase in the Hippo/yes-associated protein pathway, in the cochlea using the LATS1 knockout mice. LATS1 was expressed in hair cells and supporting cells. It was strongly expressed on the surface of the cuticular plate of the organ of Corti. We found that LATS1 knockout caused congenital hearing loss due to the irregular orientation and slightly reduced number of hair cells, whereas the number of supporting cells remained unchanged. On the surface of the hair cells, the kinocilium and stereocilia were dispersed during and after morphogenesis. However, the expression of the receptor-independent polarity regulators, such as Par3 or Gai, was not affected. We concluded that LATS1 has an indispensable role in the maturation of mammalian auditory hair cells, but not in the development of the supporting cells, and thus, has a role in the hearing acquisition. (c) 2020 Elsevier Inc. All rights reserved.