Centre for Craniofacial and Regenerative Biology, King's College London, 27th Floor, Guy's Tower, London SE1 9RT, UK.
UCL Ear Institute, University College London, 332 Gray's Inn Rd, London WC1X 8EE, UK.
Development. 2024 Aug 1;151(15). doi: 10.1242/dev.202845. Epub 2024 Aug 9.
In multicellular tissues, the size and shape of cells are intricately linked with their physiological functions. In the vertebrate auditory organ, the neurosensory epithelium develops as a mosaic of sensory hair cells (HCs), and their glial-like supporting cells, which have distinct morphologies and functional properties at different frequency positions along its tonotopic long axis. In the chick cochlea, the basilar papilla (BP), proximal (high-frequency) HCs, are larger than their distal (low-frequency) counterparts, a morphological feature essential for sound perception. Mitochondrial dynamics, which constitute the equilibrium between fusion and fission, regulate differentiation and functional refinement across a variety of cell types. We investigate this as a potential mechanism for regulating the shape of developing HCs. Using live imaging in intact BP explants, we identify distinct remodelling of mitochondrial networks in proximal compared with distal HCs. Manipulating mitochondrial dynamics in developing HCs alters their normal morphology along the proximal-distal (tonotopic) axis. Inhibition of the mitochondrial fusion machinery decreased proximal HC surface area, whereas promotion of fusion increased the distal HC surface area. We identify mitochondrial dynamics as a key regulator of HC morphology in developing inner ear epithelia.
在多细胞组织中,细胞的大小和形状与其生理功能密切相关。在脊椎动物听觉器官中,神经感觉上皮发育为感觉毛细胞 (HCs) 的镶嵌物,以及其神经胶质样支持细胞,它们在其音调长轴的不同频率位置具有不同的形态和功能特性。在鸡耳蜗中,基底乳头 (BP)、近端 (高频) HCs 比其远端 (低频) 对应物更大,这是声音感知的重要形态特征。线粒体动力学构成融合和裂变之间的平衡,调节各种细胞类型的分化和功能细化。我们将其作为调节发育中的 HCs 形状的潜在机制进行研究。我们使用完整的 BP 外植体中的实时成像,确定了与远端 HCs 相比,近端 HCs 中线粒体网络的明显重塑。在发育中的 HCs 中操纵线粒体动力学会沿着近端-远端(音调)轴改变它们的正常形态。线粒体融合机制的抑制降低了近端 HC 的表面积,而促进融合则增加了远端 HC 的表面积。我们确定线粒体动力学是发育中的内耳上皮中 HC 形态的关键调节因子。