Organ sculpting by patterned extracellular matrix stiffness

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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.

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Justin Crest

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
Alba Diz-Muñoz

Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany

Competing interests
The authors declare that no competing interests exist.
Dong-Yuan Chen

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
Dan A Fletcher

Department of Bioengineering, University of California, Berkeley, Berkeley, United States

Competing interests
The authors declare that no competing interests exist.
David Bilder

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

For correspondence
bilder@berkeley.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1842-4966

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.

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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.