Mitochondrial dynamics regulate cell size in the developing cochlea
Mitochondrial dynamics regulate cell size in the developing cochlea
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线粒体动力学调节发育中耳蜗的细胞大小
DOI：
10.1101/2024.03.04.583298
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
O'Sullivan J
中科院分区：
文献类型：
--
作者：
O'Sullivan J
在多细胞组织中，细胞的大小和形状与生理功能有着复杂的联系。在脊椎动物的听觉器官中，神经感觉上皮是由感觉毛细胞（HCs）及其胶质样支持细胞（SCs）的嵌合体发育而成的，它们在其同种异位长轴上的不同频率位置具有不同的形态。在小鸡耳蜗中，基底乳头（BP），近端（高频）hc比远端（低频）hc大，这是频率调谐所必需的形态学特征。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完善。我们研究了在hcc发育过程中细胞大小调节的潜在机制。利用完整BP外植体的实时成像，我们发现与远端hcc相比，近端hcc的线粒体网络有明显的重构。在发展hcc的过程中，操纵线粒体动力学改变了它们沿近端-远端（张力异位）轴的正常形态。抑制线粒体融合机制减少近端HC的大小，而促进融合增加远端HC的大小。我们发现线粒体动力学是内耳上皮发育过程中HC大小和形态的关键调节因子。线粒体重塑驱动听觉上皮细胞大小的发育变化。我们的数据揭示了在发育中的耳蜗中调节细胞大小和频率位置编码的基本机制。
In multicellular tissues, cell size and shape are intricately linked with physiological function. In the vertebrate auditory organ, the neurosensory epithelium develops as a mosaic of sensory hair cells (HCs), and their glial-like supporting cells (SCs), which have distinct morphologies 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 frequency tuning. Mitochondrial dynamics, which constitute the equilibrium between fusion and fission, regulate differentiation and functional refinement across a variety of cell types. We investigate this a potential mechanism for cell size regulation in developing HCs. Using live imaging in intact BP explants, we identify distinct remodelling of mitochondrial networks in proximal compared to 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 size, whilst promotion of fusion increased the distal HC size. We identify mitochondrial dynamics as a key regulator of HC size and morphology in developing inner ear epithelia.Summary StatementMitochondrial remodelling drives developmental changes in cell size in the auditory sensory epithelium. Our data reveal a fundamental mechanism regulating cell size and frequency-place coding in the developing cochlea.
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影响因子：
8
作者：
Baek, Mokryun L.;Lee, Junegoo;Pendleton, Katherine E.;Berner, Mariah J.;Goff, Emily B.;Tan, Lin;Martinez, Sara A.;Mahmud, Iqbal;Wang, Tao;Meyer, Matthew D.;Lim, Bora;Barrish, James P.;Porter, Weston;Lorenzi, Philip L.;Echeverria, Gloria V.
通讯作者：
Echeverria, Gloria V.
影响因子：
48
作者：
Schindelin, Johannes;Arganda-Carreras, Ignacio;Frise, Erwin;Kaynig, Verena;Longair, Mark;Pietzsch, Tobias;Preibisch, Stephan;Rueden, Curtis;Saalfeld, Stephan;Schmid, Benjamin;Tinevez, Jean-Yves;White, Daniel James;Hartenstein, Volker;Eliceiri, Kevin;Tomancak, Pavel;Cardona, Albert
通讯作者：
Cardona, Albert
对完整细胞中的线粒体功能进行成像。
影响因子：
--
作者：
M. Duchen;A. Surin;J. Jacobson
通讯作者：
J. Jacobson
影响因子：
5.3
作者：
R. Goodyear;G. Richardson
通讯作者：
G. Richardson