Foldi, IstvanAnthoney, NikiHarrison, NealeGangloff, MoniqueVerstak, BrettPonnadai Nallasivan, MohanakarthikAlAhmed, SamaherZhu, BangfuPhizacklea, MarkLosada Pérez, María De La PalomaMoreira, MartaGay, NicholasHidalgo, Alicia2024-08-212024-08-212017-04-03Foldi, I., Anthoney, N., Harrison, N., Gangloff, M., Verstak, B., Nallasivan, M. P., AlAhmed, S., Zhu, B., Phizacklea, M., Losada-Perez, M., Moreira, M., Gay, N. J., & Hidalgo, A. (2017). Three-tier regulation of cell number plasticity by neurotrophins and Tolls in Drosophila. The Journal of Cell Biology, 216(5), 1421-1438. https://doi.org/10.1083/jcb.2016070980021-952510.1083/jcb.201607098https://hdl.handle.net/20.500.14352/107547Cell number plasticity is coupled to circuitry in the nervous system, adjusting cell mass to functional requirements. In mammals, this is achieved by neurotrophin (NT) ligands, which promote cell survival via their Trk and p75NTR receptors and cell death via p75NTR and Sortilin. Drosophila NTs (DNTs) bind Toll receptors instead to promote neuronal survival, but whether they can also regulate cell death is unknown. In this study, we show that DNTs and Tolls can switch from promoting cell survival to death in the central nervous system (CNS) via a three-tier mechanism. First, DNT cleavage patterns result in alternative signaling outcomes. Second, different Tolls can preferentially promote cell survival or death. Third, distinct adaptors downstream of Tolls can drive either apoptosis or cell survival. Toll-6 promotes cell survival via MyD88-NF-κB and cell death via Wek-Sarm-JNK. The distribution of adaptors changes in space and time and may segregate to distinct neural circuits. This novel mechanism for CNS cell plasticity may operate in wider contexts.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article1540-8140https://doi.org/10.1083/jcb.201607098open access576612.8Cell death and autophagyDevelopmentNeuroscienceBiología celular (Biología)Neurociencias (Biológicas)2407 Biología Celular2490 Neurociencias