Abstract
Cell competition employs comparisons of fitness to selectively eliminate cells sensed as less healthy. In Drosophila, apoptotic elimination of the weaker "loser" cells from growing wing discs is induced by a signaling module consisting of the Toll ligand Spätzle (Spz), several Toll-related receptors, and NF-κB factors. How this module is activated and restricted to competing disc cells is unknown. Here, we use Myc-induced cell competition to demonstrate that loser cell elimination requires local wing disc synthesis of Spz. We identify Spz processing enzyme (SPE) and modular serine protease (ModSP) as activators of Spz-regulated competitive signaling and show that "winner" cells trigger elimination of nearby WT cells by boosting SPE production. Moreover, Spz requires both Toll and Toll-8 to induce apoptosis of wing disc cells. Thus, during cell competition, Spz-mediated signaling is strictly confined to the imaginal disc, allowing errors in tissue fitness to be corrected without compromising organismal physiology.
Citations
Nov 20, 2018·ELife·Federico GermaniKonrad Basler
Mar 7, 2019·Open Biology·Noelia PinalGinés Morata
Jun 23, 2019·G3 : Genes - Genomes - Genetics·Poojitha SitaramErika A Bach
Jan 15, 2020·Nature Reviews. Cancer·Medhavi Vishwakarma, Eugenia Piddini
Jul 18, 2020·Cancer Science·Hiroshi Kanda, Tatsushi Igaki
Sep 4, 2019·Disease Models & Mechanisms·Ketu Mishra-GorurTian Xu
Mar 17, 2020·Cell Division·Zhuojie LiLei Xue
Nov 7, 2019·Journal of Biomedical Science·Chiung-Ya ChenYi-Ping Hsueh
Jun 11, 2020·International Journal of Molecular Sciences·Francesca DestefanisPaola Bellosta
May 8, 2020·Nature Communications·Agnes R Banreti, Pascal Meier
Jul 7, 2019·Development·Sarah BowlingTristan A Rodríguez
Aug 12, 2020·Nature Reviews. Genetics·Nicholas E Baker
Nov 1, 2020·G3 : Genes - Genomes - Genetics·Albana KodraLaura A Johnston
Sep 24, 2019·Developmental Cell·Rina NagataTatsushi Igaki
Dec 31, 2020·ELife·Robert KrautzUlrich Theopold
Mar 24, 2021·Developmental Biology·Mariana Marques-Reis, Eduardo Moreno
Mar 31, 2021·Briefings in Functional Genomics·Michail Paraskevopoulos, Alison P McGuigan
Mar 30, 2021·Developmental Biology·Ginés Morata
May 2, 2021·Developmental Cell·Jules LavalouThomas Lecuit
May 14, 2021·Developmental Biology·Masazumi Tada
Jul 23, 2021·BMC Genomics·Letícia Ferreira LimaRenata Schama
Aug 10, 2021·The EMBO Journal·Taylor M ParkerRajan Gogna
Dec 7, 2021·PLoS Genetics·Naotaka OchiTatsushi Igaki