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Distinct modes of cell competition shape mammalian tissue morphogenesis
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Journal Article
Distinct modes of cell competition shape mammalian tissue morphogenesis
2019
Overview
Cell competition—the sensing and elimination of less fit ‘loser’ cells by neighbouring ‘winner’ cells—was first described in
Drosophila
. Although cell competition has been proposed as a selection mechanism to optimize tissue and organ development, its evolutionary generality remains unclear. Here, by using live imaging, lineage tracing, single-cell transcriptomics and genetics, we identify two cell competition mechanisms that sequentially shape and maintain the architecture of stratified tissue during skin development in mice. In the single-layered epithelium of the early embryonic epidermis, winner progenitors kill and subsequently clear neighbouring loser cells by engulfment. Later, as the tissue begins to stratify, the basal layer instead expels losers through upward flux of differentiating progeny. This cell competition switch is physiologically relevant: when it is perturbed, so too is barrier formation. Our findings show that cell competition is a selective force that optimizes vertebrate tissue function, and illuminate how a tissue dynamically adjusts cell competition strategies to preserve fitness as its architectural complexity increases during morphogenesis.
Cell competition in the developing mouse epithelium involves apoptosis and engulfment when the epithelium has only one layer, but switches to involve asymmetric cell division and differentiation of ‘loser’ cells as the epithelium becomes stratified.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/2
/ 14/19
/ 38/91
/ 64/60
/ Animals
/ Cloning
/ Drosophila melanogaster - cytology
/ Drosophila melanogaster - embryology
/ Epidermal Cells - metabolism
/ Female
/ Fitness
/ Genetics
/ Humanities and Social Sciences
/ Insects
/ Male
/ Mammals
/ Mice
/ Mutation
/ Progeny
/ RNA-Seq
/ Science
/ Skin
/ Tissues
