USC Caruso Department of Otolaryngology-Head and Neck Surgery, Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA, USA.
J Assoc Res Otolaryngol. 2023 Jun;24(3):291-303. doi: 10.1007/s10162-023-00894-2. Epub 2023 Mar 17.
Nuclear position is precisely orchestrated during cell division, migration, and maturation of cells and tissues. Here we report a previously unrecognized, programmed movement of the nucleus in rat and mouse cochlear inner hair cells (IHCs) coinciding with the functional maturation of inner hair cells around the onset of hearing.
We measured hair cell length and nuclear position from confocal scans of immunofluorescence-labeled hair cells from whole-mount cochlear preparations throughout post-natal development.
In early post-natal days, the IHC experiences a period of sustained growth, during which the nucleus sits at the very basal pole of the cell, far from the apically located mechano-transducing stereocilia, but close to where synapses with primary afferent and efferent neurons are forming. After IHCs reach their final length, the nucleus moves to occupy a new position half-way along the length of the cell. Nuclear translocation begins in the middle turn, completes throughout the cochlea within 2-3 days, and coincides with the emergence of endolymphatic potential, the acquisition of big-conductance potassium channels (BK), and the onset of acoustic hearing. IHCs cultured in-vitro without endolymphatic potential (EP) do not grow, do not express BK, and do not experience nuclear movement. IHCs cultured in high K+ solutions (to simulate EP) grow but do not experience nuclear movement or acquire BK channels.
Nuclear migration at the onset of hearing is a key step in the morphological maturation of IHCs. Whether this plays a role in functional maturation remains to be explored.
细胞核在细胞分裂、迁移和成熟过程中的位置是精确协调的。在这里,我们报告了一个以前未被认识到的、程序性的细胞核运动,这种运动发生在大鼠和小鼠耳蜗内毛细胞(IHC)中,与内毛细胞在听力开始时的功能成熟相吻合。
我们通过对整个出生后发育过程中来自全耳蜗制备物的免疫荧光标记的毛细胞的共焦扫描,测量了毛细胞的长度和细胞核的位置。
在出生后的早期,内毛细胞经历了一个持续生长的时期,在此期间,细胞核位于细胞的基底极,远离位于顶部的机械转导静纤毛,但靠近与初级传入和传出神经元形成突触的位置。在内毛细胞达到最终长度后,细胞核移动到细胞长度的一半处占据一个新的位置。核易位始于中阶,在 2-3 天内在整个耳蜗内完成,并与内淋巴电位的出现、大电导钾通道(BK)的获得以及听觉的出现相吻合。在没有内淋巴电位(EP)的情况下在体外培养的 IHC 不会生长,不会表达 BK,也不会经历核运动。在高 K+溶液中培养的 IHC(模拟 EP)生长,但不会经历核运动或获得 BK 通道。
听觉开始时的核迁移是 IHC 形态成熟的关键步骤。这是否在功能成熟中发挥作用还有待探讨。