Wanner Sarah J, Miller Jeffrey R
Department of Genetics, Cell Biology and Development and Developmental Biology Center, University of Minnesota, Minneapolis, MN 55455, USA.
J Cell Sci. 2007 Aug 1;120(Pt 15):2641-51. doi: 10.1242/jcs.004556. Epub 2007 Jul 17.
The inner ear is derived from a thickening in the embryonic ectoderm, called the otic placode. This structure undergoes extensive morphogenetic movements throughout its development and gives rise to all components of the inner ear. Ena/VASP-like (Evl) is an actin binding protein involved in the regulation of cytoskeletal dynamics and organization. We have examined the role of Evl during the morphogenesis of the Xenopus inner ear. Evl (hereafter referred to as Xevl) is expressed throughout otic vesicle formation and is enriched in the neuroblasts that delaminate to form the vestibulocochlear ganglion and in hair cells that possess mechanosensory stereocilia. Knockdown of Xevl perturbs epithelial morphology and intercellular adhesion in the otic vesicle and disrupts formation of the vestibulocochlear ganglion, evidenced by reduction of ganglion size, disorganization of the ganglion, and defects in neurite outgrowth. Later in embryogenesis, Xevl is required for development of mechanosensory hair cells. In Xevl knockdown embryos, hair cells of the ventromedial sensory epithelium display multiple abnormalities including disruption of the cuticular plate at the base of stereocilia and disorganization of the normal staircase appearance of stereocilia. Based on these data, we propose that Xevl plays an integral role in regulating morphogenesis of the inner ear epithelium and the subsequent development of the vestibulocochlear ganglion and mechanosensory hair cells.
内耳起源于胚胎外胚层的增厚部分,称为耳基板。该结构在其整个发育过程中经历广泛的形态发生运动,并产生内耳的所有组成部分。Ena/VASP样蛋白(Evl)是一种肌动蛋白结合蛋白,参与细胞骨架动力学和组织的调节。我们研究了Evl在非洲爪蟾内耳形态发生过程中的作用。Evl(以下简称Xevl)在耳泡形成过程中全程表达,并在分层形成前庭蜗神经节的神经母细胞和具有机械感觉静纤毛的毛细胞中富集。敲低Xevl会扰乱耳泡中的上皮形态和细胞间黏附,并破坏前庭蜗神经节的形成,这表现为神经节尺寸减小、神经节紊乱以及神经突生长缺陷。在胚胎发育后期,Xevl是机械感觉毛细胞发育所必需的。在敲低Xevl的胚胎中,腹内侧感觉上皮的毛细胞表现出多种异常,包括静纤毛基部的角质板破坏以及静纤毛正常阶梯状外观的紊乱。基于这些数据,我们提出Xevl在调节内耳上皮的形态发生以及随后前庭蜗神经节和机械感觉毛细胞的发育中起不可或缺的作用。