Spatial mapping of tissue properties in vivo reveals a 3D stiffness gradient in the mouse limb bud
- 18 February 2020
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 117 (9), 4781-4791
- https://doi.org/10.1073/pnas.1912656117
Abstract
Numerous hypotheses invoke tissue stiffness as a key parameter that regulates morphogenesis and disease progression. However, current methods are insufficient to test hypotheses that concern physical properties deep in living tissues. Here we introduce, validate, and apply a magnetic device that generates a uniform magnetic field gradient within a space that is sufficient to accommodate an organ-stage mouse embryo under live conditions. The method allows rapid, nontoxic measurement of the three-dimensional (3D) spatial distribution of viscoelastic properties within mesenchyme and epithelia. Using the device, we identify an anteriorly biased mesodermal stiffness gradient along which cells move to shape the early limb bud. The stiffness gradient corresponds to a Wnt5a-dependent domain of fibronectin expression, raising the possibility that durotaxis underlies cell movements. Three-dimensional stiffness mapping enables the generation of hypotheses and potentially the rigorous testing of mechanisms of development and disease.Keywords
Funding Information
- Gouvernement du Canada | Canadian Institutes of Health Research (137092)
- Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (00)
- Canada Research Chairs (RGPIN-2018-06061)
This publication has 63 references indexed in Scilit:
- Wnt5a stimulates chemotactic migration and chemokine production in human neutrophilsExperimental & Molecular Medicine, 2013
- Physical Biology Returns to MorphogenesisScience, 2012
- WNT5A/JNK and FGF/MAPK Pathways Regulate the Cellular Events Shaping the Vertebrate Limb BudCurrent Biology, 2010
- Oriented cell motility and division underlie early limb bud morphogenesisDevelopment, 2010
- WNT5A Is a Regulator of Fibroblast Proliferation and Resistance to ApoptosisAmerican Journal of Respiratory Cell and Molecular Biology, 2009
- Material properties of the cell dictate stress-induced spreading and differentiation in embryonic stem cellsNature Materials, 2009
- Cadherin Adhesion, Tissue Tension, and Noncanonical Wnt Signaling Regulate Fibronectin Matrix OrganizationDevelopmental Cell, 2009
- Single-molecule force spectroscopy: optical tweezers, magnetic tweezers and atomic force microscopyNature Methods, 2008
- Modeling sporadic loss of heterozygosity in mice by using mosaic analysis with double markers (MADM)Proceedings of the National Academy of Sciences of the United States of America, 2007
- Conditional and inducible transgene expression in mice through the combinatorial use of Cre-mediated recombination and tetracycline inductionNucleic Acids Research, 2005