Collagen polarization promotes epithelial elongation by stimulating locoregional cell proliferation

eLife

Jessica L Teo¹  Samantha J Stehbens¹  Hiroko Katsuno-Kambe¹  Robert J Ju¹  Alpha S Yap¹  James Hudson² 

[1] Division of Cell and Developmental Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia;QIMR Berghofer Medical Research Institute, Brisbane, Australia;

关键词: epithelia;    elongation;    tubulogenesis;    symmetry breaking;    collagen 1;    anisotropy;    Human;   

DOI  :  10.7554/eLife.67915

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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 β1-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.

【 授权许可】

CC BY