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.
Footnotes
The authors report no conflict of interest.
This work was supported by a grant to J.F.B from the Natural Sciences and Engineering Research Council of Canada (NSERC: RGPAS 478115-2015 and RGPIN 2015-06582) and the Canadian Institute of Health Research (CIHR: MOP-86495 and MOP-301710); C.H. is supported by a studentship of Vision Health Research Network-Fonds de Recherche du Québec- Santé (FRQ-S); J.F.B. holds a Chercheur Boursier Senior from the FRQ-S; and K.M. is supported by NIH grants DA011322 and DA021696.
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