Variations in basement membrane mechanics are linked to epithelial morphogenesis

Variations in basement membrane mechanics are linked to epithelial morphogenesis
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DOI:
10.1242/dev.152652
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发表时间:
2017-12-01
期刊:
影响因子:
4.6
通讯作者:
Grammont, Muriel
Grammont, Muriel
中科院分区:
生物学2区
文献类型:
--
作者:
Chlasta, Julien;Milani, Pascale;Grammont, Muriel

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基底膜(BM)对形态发生的调控可能依赖于其力学性能的变化。为了验证这一点,我们开发了一种基于原子力显微镜的方法来测量果蝇卵巢卵泡发育两个关键过程中的BM机械刚度。首先,卵泡伸长取决于上皮细胞的集体迁移,分泌BM原纤维垂直于前后轴。我们的数据表明,BM的刚度在这种迁移过程中增加,纤维的掺入增强了BM的刚度。此外,由于定向原纤维的刚度不均一性,对卵的伸长很重要。其次,上皮细胞的形状由立方体变为鳞状或柱状。我们证明BM在鳞状细胞周围软化,并且这种软化依赖于TGF β途径。我们还证明了BM成分之间的相互作用是细胞扁平化所必需的。总之,这些结果表明,BM的机械性能在发育过程中被修改,反过来,这种机械修改影响细胞和组织的形状。
The regulation of morphogenesis by the basement membrane (BM) may rely on changes in its mechanical properties. To test this, we developed an atomic force microscopy-based method to measure BM mechanical stiffness during two key processes in Drosophila ovarian follicle development. First, follicle elongation depends on epithelial cells that collectively migrate, secreting BM fibrils perpendicularly to the anteroposterior axis. Our data show that BM stiffness increases during this migration and that fibril incorporation enhances BM stiffness. In addition, stiffness heterogeneity, due to oriented fibrils, is important for egg elongation. Second, epithelial cells change their shape from cuboidal to either squamous or columnar. We prove that BM softens around the squamous cells and that this softening depends on the TGF beta pathway. We also demonstrate that interactions between BM constituents are necessary for cell flattening. Altogether, these results show that BM mechanical properties are modified during development and that, in turn, such mechanical modifications influence both cell and tissue shapes.