{"doi":"10.3410/f.714897826.793571352","title":"Faculty Opinions recommendation of Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia.","abstract":"For an epithelium to provide a protective barrier, it must maintain homeostatic cell numbers by matching the number of dividing and dying cells. While compensatory cell division can be triggered by dying cells 1-3 , how cell death might relieve overcrowding due to proliferation is not known. When we trigger apoptosis in epithelia, dying cells are extruded to preserve a functional barrier 4 . To extrude, cells destined to die signal surrounding epithelial cells to contract an actomyosin ring that squeezes the dying cell out 4-6 . However, it is not clear what drives cell death during normal homeostasis. We show that overcrowding, due to proliferation and migration, induces extrusion of live cells to control epithelial cell numbers. Live cell extrusion occurs at sites where highest crowding occurs in vivo and can be induced by experimentally overcrowding monolayers in vitro. Like apoptotic cell extrusion, live cell extrusion resulting from overcrowding also requires Sphingosine 1-Phosphate (S1P) signalling and ROCK-dependent myosin contraction but is distinguished by signalling through stretch-activated channels. Moreover, disruption of a stretch-activated channel, Piezo1, in zebrafish prevents extrusion and leads to the formation of epithelial cell masses. Our findings reveal that during homeostatic turnover, growth and division of epithelial cells on a confined substratum causes overcrowding that leads to their extrusion and consequent death due to loss of survival factors. These results suggest that live Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/","journal":"Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature","year":2020,"id":132994,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":431681,"name":"Anne K. Voss","orcid":"0000-0002-3853-9381","position":0,"is_corresponding":true}],"reference_count":23,"raw_metadata":null,"created_at":"2026-07-18T23:16:14.071209Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}