Prakash Anubhav, Weninger Julian, Singh Nishant, Raman Sukanya, Rao Madan, Kruse Karsten, Ladher Raj K
National Centre for Biological Sciences, Tata Institute for Fundamentals Research, GKVK PO, Bangalore, India.
Departments of Biochemistry and Theoretical Physics, University of Geneva, Geneva, Switzerland.
Nat Commun. 2025 Apr 26;16(1):3927. doi: 10.1038/s41467-025-58557-0.
Tissue function depends on the precise organisation of the constituent cells. In the cochlea, the fidelity of hearing depends on mechanosensory hair cells being consistently surrounded by supporting cells. In addition to this positional order, auditory sensitivity depends crucially on planar cell polarity. This is characterised by the alignment of the orientation of eccentrically placed hair bundles on each hair cell. These two levels of order emerge simultaneously despite the cellular fluxes that occur during cochlear development. However, the link between tissue-scale cellular rearrangements and intrinsic cellular mechanisms remains unknown. By combining experimental and theoretical approaches, we find a precise force patterning underpinning positional order and planar cell polarity. This occurs through the modulation of the levels and phospho-type of the regulatory light chain of non-muscle myosin II at specific cell-cell junctions of the auditory epithelium. We propose that the control of junctional mechanics is vital for the organisation of multi-cell-type epithelia.
组织功能取决于组成细胞的精确组织方式。在耳蜗中，听力的保真度取决于机械感觉毛细胞始终被支持细胞所包围。除了这种位置顺序外，听觉敏感性还至关重要地取决于平面细胞极性。其特征在于每个毛细胞上偏心放置的毛束方向的排列。尽管在耳蜗发育过程中会发生细胞流动，但这两种有序水平是同时出现的。然而，组织尺度的细胞重排与内在细胞机制之间的联系仍然未知。通过结合实验和理论方法，我们发现了一种精确的力模式，它是位置顺序和平面细胞极性的基础。这是通过在听觉上皮的特定细胞间连接处调节非肌肉肌球蛋白II调节轻链的水平和磷酸化类型来实现的。我们提出，连接力学的控制对于多细胞类型上皮的组织至关重要。
