title: Developmental suppression of schizophrenia-associated miR-137 alters sensorimotor function in zebrafish.
abstract: The neurodevelopmentally regulated microRNA miR-137 was strongly implicated as risk locus for schizophrenia in the most recent genome wide association study coordinated by the Psychiatric Genome Consortium (PGC). This molecule is highly conserved in vertebrates enabling the investigation of its function in the developing zebrafish. We utilized this model system to achieve overexpression and suppression of miR-137, both transiently and stably through transgenesis. While miR-137 overexpression was not associated with an observable specific phenotype, downregulation by antisense morpholino and/or transgenic expression of miR-sponge RNA induced significant impairment of both embryonic and larval touch-sensitivity without compromising overall anatomical development. We observed miR-137 expression and activity in sensory neurons including Rohon-Beard neurons and dorsal root ganglia, two neuronal cell types that confer touch-sensitivity in normal zebrafish, suggesting a role of these cell types in the observed phenotype. The lack of obvious anatomical or histological pathology in these cells, however, suggested that subtle axonal network defects or a change in synaptic function and neural connectivity might be responsible for the behavioral phenotype rather than a change in the cellular morphology or neuroanatomy.
authors.affiliation: Brain and Mind Research Institute, Sydney Medical School, University of Sydney, Camperdown, NSW, Australia.|Psychiatric Genomics Group, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Giacomotto
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle, Callaghan, NSW, Australia.
authors.forename: A P
authors.initials: AP
authors.lastname: Carroll
authors.affiliation: Brain and Mind Research Institute, Sydney Medical School, University of Sydney, Camperdown, NSW, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Rinkwitz
authors.affiliation: Psychiatric Genomics Group, Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.|Queensland Centre for Mental Health Research, University of Queensland, Brisbane, QLD, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Mowry
authors.affiliation: School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle, Callaghan, NSW, Australia.|Schizophrenia Research Institute, Sydney, NSW, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Cairns
authors.affiliation: Brain and Mind Research Institute, Sydney Medical School, University of Sydney, Camperdown, NSW, Australia.
authors.forename: T S
authors.initials: TS
authors.lastname: Becker
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D005727:Ganglia, Spinal / Q000378:metabolism / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D035683:MicroRNAs / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D010641:Phenotype; D012559:Schizophrenia / Q000235:genetics; D014110:Touch / Q000235:genetics*; D015027:Zebrafish
chemical_list: D035683:MicroRNAs