Primary cilium cAMP regulates cyclic saltatory neuronal migration at the centrosome

The primary cilium (PC) is crucial for neuronal migration but the underlying cellular mechanisms are mostly unknown. Here, we show that ciliary-produced cAMP present at the centrosome locally activates cAMP-dependent Protein Kinase A (PKA). We analyzed cAMP dynamics through biosensor live-imaging in cyclic saltatory migrating neurons of the mouse postnatal rostral migratory stream. This revealed a dynamic cAMP hotspot cyclically present at the centrosome, thus located at the basis of the PC. Genetic ablation of the PC and knock-down of the ciliary Adenylate Cyclase 3 lead to the hotspot disappearance. They also affect migration with defective centrosome/nucleus coupling leading to altered nucleokinesis, which is recapitulated by PKA genetic delocalization. We thus show that PC and centrosome act as a single signaling unit, linked by ciliary cAMP diffusion regulating the rhythmicity of saltatory migration at the centrosome. We generalized this finding to embryonic and adult migrating neurons.