Ishii Mamoru, Tateya Tomoko, Matsuda Michiyuki, Hirashima Tsuyoshi
Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
R Soc Open Sci. 2021 Dec 8;8(12):211024. doi: 10.1098/rsos.211024. eCollection 2021 Dec.
The bending of epithelial tubes is a fundamental process in organ morphogenesis, driven by various multicellular behaviours. The cochlea in the mammalian inner ear is a representative example of spiral tissue architecture where the continuous bending of the duct is a fundamental component of its morphogenetic process. Although the cochlear duct morphogenesis has been studied by genetic approaches extensively, it is still unclear how the cochlear duct morphology is physically formed. Here, we report that nuclear behaviour changes are associated with the curvature of the pseudostratified epithelium during murine cochlear development. Two-photon live-cell imaging reveals that the nuclei shuttle between the luminal and basal edges of the cell is in phase with cell-cycle progression, known as interkinetic nuclear migration, in the flat region of the pseudostratified epithelium. However, the nuclei become stationary on the luminal side following mitosis in the curved region. Mathematical modelling together with perturbation experiments shows that this nuclear stalling facilitates luminal-basal differential growth within the epithelium, suggesting that the nuclear stalling would contribute to the bending of the pseudostratified epithelium during the cochlear duct development. The findings suggest a possible scenario of differential growth which sculpts the tissue shape, driven by collective nuclear dynamics.
上皮管的弯曲是器官形态发生中的一个基本过程，由多种多细胞行为驱动。哺乳动物内耳中的耳蜗是螺旋组织结构的一个典型例子，其中管道的持续弯曲是其形态发生过程的一个基本组成部分。尽管通过遗传学方法对耳蜗管形态发生进行了广泛研究，但耳蜗管形态是如何通过物理方式形成的仍不清楚。在此，我们报告在小鼠耳蜗发育过程中，核行为变化与假复层上皮的曲率相关。双光子活细胞成像显示，在假复层上皮的平坦区域，细胞核在细胞腔和基底边缘之间穿梭与细胞周期进程同步，这被称为核间运动迁移。然而，在弯曲区域，细胞核在有丝分裂后在腔侧静止。数学建模和扰动实验表明，这种核停滞促进了上皮内的腔 - 基底差异生长，这表明核停滞有助于耳蜗管发育过程中假复层上皮的弯曲。这些发现提示了一种由集体核动力学驱动的差异生长塑造组织形状的可能情况。
