TY - JOUR T1 - Role of GPR55 during axon growth and target innervation JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0011-15.2015 SP - ENEURO.0011-15.2015 AU - Hosni Cherif AU - Anteneh Argaw AU - Bruno Cécyre AU - Alex Bouchard AU - Jonathan Gagnon AU - Pasha Javadi AU - Sébastien Desgent AU - Ken Mackie AU - Jean-François Bouchard Y1 - 2015/10/22 UR - http://www.eneuro.org/content/early/2015/10/22/ENEURO.0011-15.2015.abstract N2 - 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 knockout (gpr55-/- ) mouse embryos have smaller GCs, less GC filopodia, and have a decreased outgrowth compared to gpr55+/+ neurons. When gpr55+/+ neurons were treated with GPR55 agonists, LPI and O-1602, we observed a chemo-attractive effect and an increase in GC size and filopodia number. In contrast, CBD decreased the GC size and filopodia number inducing chemo-repulsion. In absence of the receptor (gpr55-/-) no pharmacological effects of the GPR55 ligands were observed. In vivo, compared to their wildtype (WTs) 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 while treatment with cannabidiol (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.Significance Statement: The implication of a novel G-protein coupled receptor, GPR55, in neurodevelopment allows the identification of new potential therapeutic targets for abnormal development and regeneration of the Central Nervous System (CNS). ER -