Collagen polarization promotes epithelial elongation by stimulating locoregional cell proliferation
- The University of Queensland, Australia
- QIMR Berghofer Medical Research Institute, Australia
Abstract
Epithelial networks are commonly generated by processes where multicellular aggregates elongate and branch. Here we focus on understanding cellular mechanisms for elongation, using an organotypic culture system as a model of mammary epithelial anlage. Isotropic cell aggregates broke symmetry and slowly elongated when transplanted into collagen 1 gels. The elongating regions of aggregates displayed enhanced cell proliferation that was necessary for elongation to occur. Strikingly, this loco-regional increase in cell proliferation occurred where collagen 1 fibrils reorganized into bundles which were polarized with the elongating aggregates. Applying external stretch as a cell-independent way to reorganize the ECM, we found that collagen polarization stimulated regional cell proliferation to precipitate symmetry-breaking and elongation. This required b1-integrin and ERK signaling. We propose that collagen polarization supports epithelial anlagen elongation by stimulating loco-regional cell proliferation. This could provide a long-lasting structural memory of the initial axis that is generated when anlage break symmetry.
Data availability
All data generated and analysed in this study are included in the manuscript and supporting files. Source data files have been provided for Figure 1-7.
Article and author information
Author details
Hiroko Katsuno-Kambe
Samantha J Stehbens
Funding
National Health and Medical Research Council (Fellowship 1136592)
- Alpha S Yap
National Health and Medical Research Council (GNT1123816)
- Alpha S Yap
National Health and Medical Research Council (1140090)
- Alpha S Yap
Australian Research Council (DP19010287)
- Alpha S Yap
Australian Research Council (190102230)
- Alpha S Yap
Australian Research Council (FT190100516)
- Samantha J Stehbens
Snow Medical Fellowship
- James Hudson
Uehara Memorial Foundation (Postdoctoral fellowship)
- Hiroko Katsuno-Kambe
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Katsuno-Kambe 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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Collagen polarization promotes epithelial elongation by stimulating locoregional cell proliferation
eLife 10:e67915.
https://doi.org/10.7554/eLife.67915
