Journal
ELIFE
Volume 10, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.67915
Keywords
epithelia; elongation; tubulogenesis; symmetry breaking; collagen 1; anisotropy; Human
Categories
Funding
- National Health and Medical Research Council [1136592, GNT1123816, 1140090]
- Australian Research Council [DP19010287, 190102230, FT190100516]
- Snow Medical Fellowship Foundation Postdoctoral fellowship
- National Health and Medical Research Council of Australia [1136592, 1140090] Funding Source: NHMRC
- Australian Research Council [FT190100516] Funding Source: Australian Research Council
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The study found that collagen 1 polarization can stimulate regional cell proliferation, leading to symmetry breaking and elongation. This process requires the involvement of beta 1-integrin and ERK signaling. Collagen polarization supports elongation of epithelial anlage and may provide a lasting structural memory.
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 locoregional increase in cell proliferation occurred where collagen 1 fibrils reorganized into bundles that were polarized with the elongating aggregates. Applying external stretch as a cell-independent way to reorganize the extracellular matrix, we found that collagen polarization stimulated regional cell proliferation to precipitate symmetry breaking and elongation. This required beta 1-integrin and ERK signaling. We propose that collagen polarization supports epithelial anlagen elongation by stimulating locoregional cell proliferation. This could provide a long-lasting structural memory of the initial axis that is generated when anlage break symmetry.
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