Institute of Biochemistry I, Jena University Hospital - Friedrich Schiller University Jena, 07743 Jena, Germany.
EM Center, Jena University Hospital - Friedrich Schiller University Jena, 07743 Jena, Germany.
Cell Rep. 2018 Aug 28;24(9):2418-2431.e6. doi: 10.1016/j.celrep.2018.07.087.
Proper cochlear hair cell array development and sensory apparatus positioning are achieved by planar cell polarity signaling. Effectors executing proper tissue development and maturation programs are largely unknown. We show that the actin nucleator Cobl is an important effector in postnatal refinement and maintenance of planar cell polarity. During the critical time of hearing onset, these polarity defects coincided with reduced F-actin beneath the sensory apparatus and with premature kinocilium retraction. These defects were accompanied by organizational defects of the pericentriolar scaffold that coincided with basal body and centriolar mispositionings. Importantly, the pericentriolar defects observed in Cobl KO mice were demonstrated to be actin polymerization dependent and calcium/calmodulin signaling dependent. Because Cobl KO phenotypes manifested postnatally, planar cell polarity is not solely an important developmental process. The Cobl-dependent planar cell polarity maintenance and refinement processes we describe here seem critical for hearing, as Cobl KO mice show deficient cochlear amplification.
通过平面细胞极性信号转导实现了适当的耳蜗毛细胞阵列发育和感觉器官定位。执行适当组织发育和成熟程序的效应物在很大程度上是未知的。我们表明，肌动蛋白核因子 Cobl 是后生期平面细胞极性的精细调整和维持的重要效应物。在听力起始的关键时期，这些极性缺陷与感觉器官下的 F-肌动蛋白减少以及动纤毛过早回缩同时发生。这些缺陷伴随着中心粒支架的组织缺陷，与基底体和中心粒的错位同时发生。重要的是，在 Cobl KO 小鼠中观察到的中心粒缺陷被证明是肌动蛋白聚合依赖性和钙/钙调蛋白信号依赖性的。由于 Cobl KO 表型在出生后表现出来，因此平面细胞极性不仅仅是一个重要的发育过程。我们在这里描述的 Cobl 依赖性平面细胞极性维持和细化过程似乎对听力很重要，因为 Cobl KO 小鼠表现出耳蜗放大功能缺陷。
