Organ sculpting by patterned extracellular matrix stiffness

Author:

Crest Justin1ORCID,Diz-Muñoz Alba2,Chen Dong-Yuan1,Fletcher Daniel A2,Bilder David1ORCID

Affiliation:

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

2. Department of Bioengineering and Biophysics Program, University of California-Berkeley, Berkeley, United States

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 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.

Funder

National Institutes of Health

Damon Runyon Cancer Research Foundation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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