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细胞与细胞外基质黏附的局部减弱引发基底上皮组织折叠。

Local weakening of cell-extracellular matrix adhesion triggers basal epithelial tissue folding.

作者信息

Valencia-Expósito Andrea, Khalilgharibi Nargess, Martínez-Abarca Millán Ana, Mao Yanlan, Martín-Bermudo María D

机构信息

Centro Andaluz de Biología del Desarrollo CSIC-Univ. Pablo de Olavide, Sevilla, 41013, Spain.

Laboratory for Molecular Cell Biology, University College London, Gower Street, London, WC1E 6BT, UK.

出版信息

EMBO J. 2025 Apr;44(7):2002-2024. doi: 10.1038/s44318-025-00384-6. Epub 2025 Feb 17.

Abstract

During development, epithelial sheets sculpt organs by folding, either apically or basally, into complex 3D structures. Given the presence of actomyosin networks and cell adhesion sites on both sides of cells, a common machinery mediating apical and basal epithelial tissue folding has been proposed. However, unlike for apical folding, little is known about the mechanisms that regulate epithelial folding towards the basal side. Here, using the Drosophila wing imaginal disc and combining genetic perturbations and computational modeling, we demonstrate opposing roles for cell-cell and cell-extracellular matrix (ECM) adhesion systems during epithelial folding. While cadherin-mediated adhesion, linked to actomyosin network, regulates apical folding, a localized reduction on integrin-dependent adhesion, followed by changes in cell shape and reorganization of the basal actomyosin cytoskeleton and E-Cadherin (E-Cad) levels, is necessary and sufficient to trigger basal folding. These results suggest that modulation of the cell mechanical landscape through the crosstalk between integrins and cadherins is essential for correct epithelial folding.

摘要

在发育过程中,上皮细胞层通过向顶端或基底折叠,塑造出复杂的三维器官结构。鉴于细胞两侧均存在肌动球蛋白网络和细胞黏附位点,人们提出了一种介导顶端和基底上皮组织折叠的通用机制。然而,与顶端折叠不同的是,关于调控上皮细胞向基底侧折叠的机制,我们知之甚少。在这里,我们利用果蝇翅成虫盘,结合基因扰动和计算模型,证明了细胞-细胞和细胞-细胞外基质(ECM)黏附系统在上皮细胞折叠过程中发挥着相反的作用。虽然与肌动球蛋白网络相连的钙黏蛋白介导的黏附作用调节顶端折叠,但整合素依赖性黏附的局部减少,随后细胞形状的改变以及基底肌动球蛋白细胞骨架和E-钙黏蛋白(E-Cad)水平的重新组织,对于触发基底折叠来说是必要且充分的。这些结果表明,通过整合素和钙黏蛋白之间的相互作用来调节细胞力学环境,对于上皮细胞的正确折叠至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed03/11961693/5eef426698d0/44318_2025_384_Fig1_HTML.jpg

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