Characterization of GPR17 expression in oligodendrocyte precursor cells of the postnatal and adult mouse cortex: focus on proliferation activity

The G protein coupled receptor GPR17 has been shown to have an important role in regulating the stage of oligodendrocyte precursor cells (OPCs) differentiation in vitro and in vivo during postnatal brain myelination. GPR17 is expressed on OPCs during development and adulthood, and its expression decreases with maturation of OPCs. To characterize the exact timing of GPR17 expression, we focused our analysis on the postnatal and adult mouse brain by using an in-house developed antibody for GPR17 and known markers for the oligodendrocyte lineage. In the mouse cortex, the receptor is present mainly on NG2-positive cells, hardly present on PDGFRa-positive cells (a marker for more immature OPCs) and is not expressed on mature oligodendrocytes, as shown by GSTπ staining. Since the functional role of GPR17 in the adult intact brain is still unknown, we investigated whether it is involved in NG2-positive cells proliferation. Since these cells are indeed the only cells able to proliferate in the adult mouse brain outside the neurogenic niches. When we administered to adult mice the thymidine analog BrdU to specifically label cells that have proliferated during BrdU exposure, we observed that only a subpopulation of the dividing cells express GPR17. Interestingly, we could also observe an increase over time of cells that have proliferated and express GPR17. When we stained for a marker of actively proliferating cells (Ki67), we could hardly see any Ki67-positive cell that expressed GPR17. These results, together with the data showing the expression of GPR17 only at a particular stage of OPC differentiation, led us to the idea that OPCs upregulate the receptor only after proliferation has taken place. This hypothesis was then confirmed by label retaining experiments, that show a transient expression of the receptor after proliferation.