title: Three-tier regulation of cell number plasticity by neurotrophins and Tolls inDrosophila.
abstract: Cell 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 p75NTRreceptors and cell death via p75NTRand Sortilin.DrosophilaNTs (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.
authors.affiliation: NeuroDevelopment Group, School of Biosciences, University of Birmingham, Birmingham B15 2TT, England, UK.
authors.forename: Istvan
authors.identifier: 0000-0002-1832-9854
authors.initials: I
authors.lastname: Foldi
authors.affiliation: NeuroDevelopment Group, School of Biosciences, University of Birmingham, Birmingham B15 2TT, England, UK.
authors.forename: Niki
authors.identifier: 0000-0003-3311-6328
authors.initials: N
authors.lastname: Anthoney
authors.affiliation: NeuroDevelopment Group, School of Biosciences, University of Birmingham, Birmingham B15 2TT, England, UK.
authors.forename: Neale
authors.identifier: 0000-0001-6821-4089
authors.initials: N
authors.lastname: Harrison
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, England, UK.
authors.forename: Monique
authors.identifier: 0000-0001-6131-0115
authors.initials: M
authors.lastname: Gangloff
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, England, UK.
authors.forename: Brett
authors.identifier: 0000-0003-1459-114X
authors.initials: B
authors.lastname: Verstak
authors.affiliation: NeuroDevelopment Group, School of Biosciences, University of Birmingham, Birmingham B15 2TT, England, UK.
authors.forename: Mohanakarthik Ponnadai
authors.identifier: 0000-0002-5244-5816
authors.initials: MP
authors.lastname: Nallasivan
authors.affiliation: NeuroDevelopment Group, School of Biosciences, University of Birmingham, Birmingham B15 2TT, England, UK.
authors.forename: Samaher
authors.identifier: 0000-0002-3299-8157
authors.initials: S
authors.lastname: AlAhmed
authors.affiliation: NeuroDevelopment Group, School of Biosciences, University of Birmingham, Birmingham B15 2TT, England, UK.
authors.forename: Bangfu
authors.identifier: 0000-0002-9325-926X
authors.initials: B
authors.lastname: Zhu
authors.affiliation: NeuroDevelopment Group, School of Biosciences, University of Birmingham, Birmingham B15 2TT, England, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Phizacklea
authors.affiliation: NeuroDevelopment Group, School of Biosciences, University of Birmingham, Birmingham B15 2TT, England, UK.
authors.forename: Maria
authors.identifier: 0000-0002-6717-7762
authors.initials: M
authors.lastname: Losada-Perez
authors.affiliation: NeuroDevelopment Group, School of Biosciences, University of Birmingham, Birmingham B15 2TT, England, UK.
authors.forename: Marta
authors.identifier: 0000-0002-4779-4077
authors.initials: M
authors.lastname: Moreira
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, England, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Gay
authors.affiliation: NeuroDevelopment Group, School of Biosciences, University of Birmingham, Birmingham B15 2TT, England, UK a.hidalgo@bham.ac.uk.
authors.forename: Alicia
authors.identifier: 0000-0001-8041-5764
authors.initials: A
authors.lastname: Hidalgo
mesh_terms: D000818:Animals; D002452:Cell Count; D016923:Cell Death; D002470:Cell Survival; D004330:Drosophila; D009414:Nerve Growth Factors / Q000378:metabolism*; D009473:Neuronal Plasticity; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D009414:Nerve Growth Factors; D051193:Toll-Like Receptors