Crest Justin, Diz-Muñoz Alba, Chen Dong-Yuan, Fletcher Daniel A, Bilder David
Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, United States.
Department of Bioengineering and Biophysics Program, University of California-Berkeley, Berkeley, United States.
Elife. 2017 Jun 27;6:e24958. doi: 10.7554/eLife.24958.
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.
器官塑造过程中的机械失衡是如何产生的，这是形态发生的核心问题，现有范式聚焦于细胞内的不对称力产生。我们在此表明，器官可以通过在其细胞外基质（ECM）中构建各向异性阻力来塑造。通过对伸长的果蝇卵室进行直接生物物理测量，我们记录到基于ECM的基底膜（BM）中存在强大的机械各向异性，而其下方的上皮组织中则不存在。对体内野生型BM进行原子力显微镜（AFM）检测，发现其存在前后（A-P）对称的刚度梯度，而在伸长缺陷型突变体中该梯度无法形成。基因操作表明，BM对组织伸长具有指导作用，决定因素是相对刚度而非绝对刚度，从而对各向同性组织扩张产生不同的阻力。刚度梯度需要类形态发生素信号来调节BM整合，以及平面极化组织来使其周向均匀化。我们的结果证明了ECM中的精细机械模式如何引导细胞塑造器官。
