Cell competition in development: information from flies and vertebrates

Growth control in the Drosophila wing disk

“…For example, wing disk cells show heterogeneous spatial patterns of cell cycle times, in which clusters of cells appear in the same phase due to local cell–cell interactions (Milán, Campuzano, & García‐Bellido, ), but cell patches at different locations of the disk show different cell cycle phases and duration (Dubatolova & Omelyanchuk, ; Milán, Campuzano, & García‐Bellido, ). As mentioned earlier, mechanical forces have been proposed as one of the important controllers of growth, and have also been suggested as mediators of cell cycle control in various systems (Schluck, Nienhaus, Aegerter‐Wilmsen, & Aegerter, ; Uroz et al, ), partially through the regulation of the Hippo components (Madan, Gogna, & Moreno, ). These will be discussed further in the next section.…”

Elimination of oncogenic cells that regulate epithelial homeostasis in Drosophila

“…For instance, oncogenic cells activating an oncogene such as Ras, Src, ErbB2, or YAP are eliminated from the epithelial layer when surrounded by wild-type cells in mammals (Chiba et al, 2016;Hogan et al, 2009;Kajita et al, 2010;Leung & Brugge, 2012). The removal of surrounding wild-type cells by genetically inducing cell death allows these polarity-deficient mutant cells to overgrow (Brumby & Richardson, 2003), suggesting that polarity-deficient cells are actively eliminated from the epithelial tissue through "competitive" interactions with surrounding wild-type cells, a form of "cell competition" (Claveria & Torres, 2016;Di Gregorio, Bowling, & Rodriguez, 2016;Madan, Gogna, & Moreno, 2018;Morata & Ripoll, 1975;Nagata & Igaki, 2018). The removal of surrounding wild-type cells by genetically inducing cell death allows these polarity-deficient mutant cells to overgrow (Brumby & Richardson, 2003), suggesting that polarity-deficient cells are actively eliminated from the epithelial tissue through "competitive" interactions with surrounding wild-type cells, a form of "cell competition" (Claveria & Torres, 2016;Di Gregorio, Bowling, & Rodriguez, 2016;Madan, Gogna, & Moreno, 2018;Morata & Ripoll, 1975;Nagata & Igaki, 2018).…”

Prostaglandin E2 and its receptor EP2 trigger signaling that contributes to YAP‐mediated cell competition

“…The YAP (5SA) mutant protein, in which these five key Ser residues are replaced with Ala, becomes constitutively active. In mouse fibroblast NIH3T3 cells, cell competition resulting in apoptosis was reportedly dependent on TEAD activity (Mamada, Sato, Ota, & Sasaki, 2015). We subsequently showed that MDCK cells and mouse hepatocytes also undergo YAP-induced competition (Chiba et al, 2016;Miyamura et al, 2017).…”

“…This observation led to the concept of "cell competition" in which a given cell compares its fitness to that of its neighboring cells. Cells with a relatively higher fitness level survive, whereas cells with a relatively lower fitness level are eliminated by either apoptosis or apical extrusion (Baker, 2017;de Beco, Ziosi, & Johnston, 2012;Bowling, Lawlor, & Rodriguez, 2019;Claveria & Torres, 2016;Madan, Gogna, & Moreno, 2018;Morata & Calleja, 2019;Wagstaff, Kolahgar, & Piddini, 2013). Cell competition is now a well-established process among mammalian "cell societies" as well.…”

“…In Drosophila, cell competition can be induced by activation of proto-oncogenes such as Myc, Ras and Src, as well as that of genes regulating cellular apicobasal polarity such as Scribble and Discs large (Dlg) (Baker, 2017;de Beco et al, 2012;Bowling et al, 2019;Claveria & Torres, 2016;Madan et al, 2018;Morata & Calleja, 2019;Nagata & Igaki, 2018;Wagstaff et al, 2013). In the developing mouse embryo, cells with low levels of Myc undergo apoptosis if in proximity to cells with higher Myc levels (Claveria, Giovinazzo, Sierra, & Torres, 2013;Sancho et al, 2013).…”