title: Drosophila neurotrophins reveal a common mechanism for nervous system formation.
abstract: Neurotrophic interactions occur in Drosophila, but to date, no neurotrophic factor had been found. Neurotrophins are the main vertebrate secreted signalling molecules that link nervous system structure and function: they regulate neuronal survival, targeting, synaptic plasticity, memory and cognition. We have identified a neurotrophic factor in flies, Drosophila Neurotrophin (DNT1), structurally related to all known neurotrophins and highly conserved in insects. By investigating with genetics the consequences of removing DNT1 or adding it in excess, we show that DNT1 maintains neuronal survival, as more neurons die in DNT1 mutants and expression of DNT1 rescues naturally occurring cell death, and it enables targeting by motor neurons. We show that Spätzle and a further fly neurotrophin superfamily member, DNT2, also have neurotrophic functions in flies. Our findings imply that most likely a neurotrophin was present in the common ancestor of all bilateral organisms, giving rise to invertebrate and vertebrate neurotrophins through gene or whole-genome duplications. This work provides a missing link between aspects of neuronal function in flies and vertebrates, and it opens the opportunity to use Drosophila to investigate further aspects of neurotrophin function and to model related diseases.
authors.affiliation: Neurodevelopment Group, School of Biosciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Bangfu
authors.initials: B
authors.lastname: Zhu
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Pennack
authors.forename: Peter
authors.initials: P
authors.lastname: McQuilton
authors.forename: Manuel G
authors.initials: MG
authors.lastname: Forero
authors.forename: Kenji
authors.initials: K
authors.lastname: Mizuguchi
authors.forename: Ben
authors.initials: B
authors.lastname: Sutcliffe
authors.forename: Chun-Jing
authors.initials: CJ
authors.lastname: Gu
authors.forename: Janine C
authors.initials: JC
authors.lastname: Fenton
authors.forename: Alicia
authors.initials: A
authors.lastname: Hidalgo
mesh_terms: D000818:Animals; D001369:Axons; D001483:Base Sequence; D016923:Cell Death; D017124:Conserved Sequence; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D008124:Locomotion; D009414:Nerve Growth Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009420:Nervous System / Q000196:embryology*; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D020539:Sequence Analysis, Protein
chemical_list: D029721:Drosophila Proteins; D009414:Nerve Growth Factors; C534531:neurotrophin 1, Drosophila; C086179:spz protein, Drosophila