- Title
- Developmental suppression of schizophrenia-associated miR-137 alters sensorimotor function in zebrafish.
- Creator
- Giacomotto, J.; Carroll, A. P.; Rinkwitz, S.; Mowry, B.; Cairns, M. J.; Becker, T. S.
- Relation
- NHMRC.1024863
- Relation
- Translational Psychiatry Vol. 6
- Publisher Link
- http://dx.doi.org/10.1038/tp.2016.88
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2016
- Description
- 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.
- Subject
- schizophrenia; microRNA miR-137; genome wide association study
- Identifier
- http://hdl.handle.net/1959.13/1323810
- Identifier
- uon:24896
- Identifier
- ISSN:2158-3188
- Rights
- This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
- Language
- eng
- Full Text
- Reviewed
- Hits: 4496
- Visitors: 4753
- Downloads: 301
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 3 MB | Adobe Acrobat PDF | View Details Download |