Organ sculpting by patterned extracellular matrix stiffness

  1. Justin Crest
  2. Alba Diz-Muñoz
  3. Dong-Yuan Chen
  4. Dan A Fletcher
  5. David Bilder  Is a corresponding author
  1. University of California, Berkeley, United States
  2. European Molecular Biology Laboratory, Germany

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

  1. 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.
  2. Alba Diz-Muñoz

    Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. 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.
  4. Dan A Fletcher

    Department of Bioengineering, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. 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.
    ORCID icon "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.

Reviewing Editor

  1. Allan C Spradling, Howard Hughes Medical Institute, Carnegie Institution for Science, United States

Publication history

  1. Received: January 20, 2017
  2. Accepted: June 7, 2017
  3. Accepted Manuscript published: June 27, 2017 (version 1)
  4. Version of Record published: July 10, 2017 (version 2)
  5. Version of Record updated: October 23, 2017 (version 3)

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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  1. Justin Crest
  2. Alba Diz-Muñoz
  3. Dong-Yuan Chen
  4. Dan A Fletcher
  5. David Bilder
(2017)
Organ sculpting by patterned extracellular matrix stiffness
eLife 6:e24958.
https://doi.org/10.7554/eLife.24958

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