Organ sculpting by patterned extracellular matrix stiffness
Abstract
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 the underlying epithelium. Atomic force microscopy (AFM) on wild-type BM in vivo reveals an 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.
Article and author information
Author details
Funding
National Institutes of Health (GM68675)
- David Bilder
Damon Runyon Cancer Research Foundation (DRG 2173-13)
- Justin Crest
National Institutes of Health (GM111111)
- David Bilder
Damon Runyon Cancer Research Foundation (DRG 2157-12)
- Alba Diz-Muñoz
National Institutes of Health (GM074751)
- Dan A Fletcher
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Crest et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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