title: Role of GPR55 during Axon Growth and Target Innervation.
abstract: Guidance molecules regulate the navigation of retinal ganglion cell (RGC) projections toward targets in the visual thalamus. In this study, we demonstrate that the G-protein-coupled receptor 55 (GPR55) is expressed in the retina during development, and regulates growth cone (GC) morphology and axon growth. In vitro, neurons obtained from gpr55 knock-out (gpr55(-/-) ) mouse embryos have smaller GCs, less GC filopodia, and have a decreased outgrowth compared with gpr55(+/+) neurons. When gpr55(+/+) neurons were treated with GPR55 agonists, lysophosphatidylinositol (LPI) and O-1602, we observed a chemo-attractive effect and an increase in GC size and filopodia number. In contrast, cannabidiol (CBD) decreased the GC size and filopodia number inducing chemo-repulsion. In absence of the receptor (gpr55(-/-) ), no pharmacologic effects of the GPR55 ligands were observed. In vivo, compared to their wild-type (WT) littermates, gpr55(-/-) mice revealed a decreased branching in the dorsal terminal nucleus (DTN) and a lower level of eye-specific segregation of retinal projections in the superior colliculus (SC) and in the dorsal lateral geniculate nucleus (dLGN). Moreover, a single intraocular injection of LPI increased branching in the DTN, whereas treatment with CBD, an antagonist of GPR55, decreased it. These results indicate that GPR55 modulates the growth rate and the targets innervation of retinal projections and highlight, for the first time, an important role of GPR55 in axon refinement during development.
authors.affiliation: School of Optometry, University of Montreal , Montreal, Quebec H3T 1P1, Canada.
authors.forename: Hosni
authors.initials: H
authors.lastname: Cherif
authors.affiliation: School of Optometry, University of Montreal, Montreal, Quebec H3T 1P1, Canada; VIB Vesalius Research Center, KU Leuven, Leuven, Belgium, 3000.
authors.forename: Anteneh
authors.initials: A
authors.lastname: Argaw
authors.affiliation: School of Optometry, University of Montreal , Montreal, Quebec H3T 1P1, Canada.
authors.forename: Bruno
authors.initials: B
authors.lastname: Cécyre
authors.affiliation: School of Optometry, University of Montreal , Montreal, Quebec H3T 1P1, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Bouchard
authors.affiliation: School of Optometry, University of Montreal , Montreal, Quebec H3T 1P1, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gagnon
authors.affiliation: School of Optometry, University of Montreal , Montreal, Quebec H3T 1P1, Canada.
authors.forename: Pasha
authors.initials: P
authors.lastname: Javadi
authors.affiliation: CHU Sainte-Justine , Montreal, Quebec H3T 1C5, Canada.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Desgent
authors.affiliation: Department of Physiological and Brain Sciences, Indiana University , Bloomington, Indiana 47405-7000.
authors.forename: Ken
authors.initials: K
authors.lastname: Mackie
authors.affiliation: School of Optometry, University of Montreal , Montreal, Quebec H3T 1P1, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bouchard
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002185:Cannabidiol / Q000031:analogs & derivatives / Q000494:pharmacology; D049108:Cell Enlargement; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D005260:Female; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology*; D008246:Lysophospholipids / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011554:Pseudopodia / Q000187:drug effects / Q000502:physiology; D043882:Receptors, Cannabinoid / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D014795:Visual Pathways / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000502:physiology
chemical_list: D002491:Central Nervous System Agents; C526692:GPR55 protein, mouse; D008246:Lysophospholipids; D043882:Receptors, Cannabinoid; C025449:lysophosphatidylinositol; D002185:Cannabidiol; C568537:O-1602 compound
keywords: GPR55 receptor; axon guidance; development; growth cone; retinal ganglion cell; vision