Cannabinoid Receptor CB2 Modulates Axon Guidance

Gabriel Duff, Anteneh Argaw, Bruno Cecyre, Hosni Cherif, Nicolas Tea, Nawal Zabouri, Christian Casanova, Maurice Ptito, Jean-François Bouchard, Alain Chédotal
2013 PLoS ONE  
Navigation of retinal projections towards their targets is regulated by guidance molecules and growth cone transduction mechanisms. Here, we present in vitro and in vivo evidences that the cannabinoid receptor 2 (CB 2 R) is expressed along the retino-thalamic pathway and exerts a modulatory action on axon guidance. These effects are specific to CB 2 R since no changes were observed in mice where the gene coding for this receptor was altered (cnr2 2/2 ). The CB 2 R induced morphological changes
more » ... bserved at the growth cone are PKA dependent and require the presence of the netrin-1 receptor, Deleted in Colorectal Cancer. Interfering with endogenous CB 2 R signalling using pharmacological agents increased retinal axon length and induced aberrant projections. Additionally, cnr2 2/2 mice showed abnormal eye-specific segregation of retinal projections in the dorsal lateral geniculate nucleus (dLGN) indicating CB 2 R's implication in retinothalamic development. Overall, this study demonstrates that the contribution of endocannabinoids to brain development is not solely mediated by CB 1 R, but also involves CB 2 R.
doi:10.1371/journal.pone.0070849 pmid:23951024 pmcid:PMC3739758 fatcat:koonrkwy4vgdxdzeu57yo36soa