Cannabinoid receptor CB2 modulates axon guidance

TY - JOUR

T1 - Cannabinoid receptor CB2 modulates axon guidance

AU - Duff, Gabriel

AU - Argaw, Anteneh

AU - Cecyre, Bruno

AU - Cherif, Hosni

AU - Tea, Nicolas

AU - Zabouri, Nawal

AU - Casanova, Christian

AU - Ptito, Maurice

AU - Bouchard, Jean-François

PY - 2013/8/9

Y1 - 2013/8/9

N2 - 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 (CB2R) is expressed along the retino-thalamic pathway and exerts a modulatory action on axon guidance. These effects are specific to CB2R since no changes were observed in mice where the gene coding for this receptor was altered (cnr2 (-/-)). The CB2R induced morphological changes observed at the growth cone are PKA dependent and require the presence of the netrin-1 receptor, Deleted in Colorectal Cancer. Interfering with endogenous CB2R signalling using pharmacological agents increased retinal axon length and induced aberrant projections. Additionally, cnr2 (-/-) mice showed abnormal eye-specific segregation of retinal projections in the dorsal lateral geniculate nucleus (dLGN) indicating CB2R's implication in retinothalamic development. Overall, this study demonstrates that the contribution of endocannabinoids to brain development is not solely mediated by CB1R, but also involves CB2R.

AB - 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 (CB2R) is expressed along the retino-thalamic pathway and exerts a modulatory action on axon guidance. These effects are specific to CB2R since no changes were observed in mice where the gene coding for this receptor was altered (cnr2 (-/-)). The CB2R induced morphological changes observed at the growth cone are PKA dependent and require the presence of the netrin-1 receptor, Deleted in Colorectal Cancer. Interfering with endogenous CB2R signalling using pharmacological agents increased retinal axon length and induced aberrant projections. Additionally, cnr2 (-/-) mice showed abnormal eye-specific segregation of retinal projections in the dorsal lateral geniculate nucleus (dLGN) indicating CB2R's implication in retinothalamic development. Overall, this study demonstrates that the contribution of endocannabinoids to brain development is not solely mediated by CB1R, but also involves CB2R.

KW - Animals

KW - Axons

KW - Cyclic AMP-Dependent Protein Kinases

KW - Embryo, Mammalian

KW - Endocannabinoids

KW - Gene Expression Regulation, Developmental

KW - Geniculate Bodies

KW - Mice

KW - Mice, Knockout

KW - Neurogenesis

KW - Primary Cell Culture

KW - Receptor, Cannabinoid, CB1

KW - Receptor, Cannabinoid, CB2

KW - Receptors, Cell Surface

KW - Retinal Ganglion Cells

KW - Visual Pathways

U2 - 10.1371/journal.pone.0070849

DO - 10.1371/journal.pone.0070849

M3 - Journal article

C2 - 23951024

SN - 1932-6203

VL - 8

SP - e70849

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 8

ER -