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.
Highlights
The G-protein-coupled receptor 55 (GPR55) is a 319amino acid protein that was identified, cloned, and mapped to human chromosome 2q37 in 1999 (Sawzdargo et al, 1999)
At P1, GPR55 protein was present in the ganglion cell (GCL), ganglion cell fibers (GCFLs), inner plexiform (IPL) and neuroblast (NBL) layers, whereas GPR55 mRNA was present in the GCL (Fig. 1A–F)
GPR55 protein was expressed in the GCL, GCFL, IPL, and NBL, whereas GPR55 mRNA was localized in GCL in retina of E14/15 mouse embryos (Fig. 1G–L)
Summary
The G-protein-coupled receptor 55 (GPR55) is a 319amino acid protein that was identified, cloned, and mapped to human chromosome 2q37 in 1999 (Sawzdargo et al, 1999). GPR55 is expressed in the CNS, as well as in intestine, bone marrow, immune and endothelial cells, spleen, and platelets (Sawzdargo et al, 1999; Ryberg et al, 2007; Waldeck-Weiemair et al, 2008; Pietr et al, 2009; Balenga et al, 2011; Henstridge et al, 2011; Rowley et al, 2011). Received January 29, 2015; accepted October 15, 2015; First published October 22, 2015. The authors report no conflict of interest.
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