Organ sculpting by patterned extracellular matrix stiffness
Organ sculpting by patterned extracellular matrix stiffness
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DOI：
10.7554/elife.24958
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发表时间：
2017-06-27
期刊：
影响因子：
7.7
通讯作者：
Bilder, David
中科院分区：
文献类型：
--
作者：
Crest, Justin;Diz-Munoz, Alba;Bilder, David
器官形成的机械不平衡是如何产生的是形态发生的一个核心问题，现有的范式集中在细胞内不对称力的产生。我们在这里表明，器官可以通过细胞外基质（ECM）内的各向异性阻力来雕刻。通过对果蝇卵室的直接生物物理测量，我们记录了基于ecm的基底膜（BM）的强大的机械各向异性，但在下层上皮中没有。野生型BM在体内的原子力显微镜（AFM）显示出一种前后对称（A-P）的刚度梯度，而这种梯度在伸长缺陷突变体中没有出现。遗传操作表明，BM对组织伸长具有指导意义，决定因素是相对而不是绝对刚度，从而对各向同性组织扩张产生差异阻力。刚度梯度需要类似形态的信号来调节BM的结合，以及平面极化组织来使其周向均匀化。我们的研究结果表明，ECM中的精细机械模式如何引导细胞形成器官。
How organ-shaping mechanical imbalances are generated is a central question of morphogenesis, with existing paradigms focusing on asymmetric force generation within cells. We show here that organs can be sculpted instead by patterning anisotropic resistance within their extracellular matrix (ECM). Using direct biophysical measurements of elongating Drosophila egg chambers, we document robust mechanical anisotropy in the ECM-based basement membrane (BM) but not in the underlying epithelium. Atomic force microscopy (AFM) on wild-type BM in vivo reveals an anterior posterior (A-P) symmetric stiffness gradient, which fails to develop in elongation-defective mutants. Genetic manipulation shows that the BM is instructive for tissue elongation and the determinant is relative rather than absolute stiffness, creating differential resistance to isotropic tissue expansion. The stiffness gradient requires morphogen-like signaling to regulate BM incorporation, as well as planar-polarized organization to homogenize it circumferentially. Our results demonstrate how fine mechanical patterning in the ECM can guide cells to shape an organ.