Expression of sorting nexin 12 is regulated in developing cerebral cortical neurons

The sorting nexins (SNXs) are a family of proteins functioning in diverse processes, including endocytosis, endosomal sorting, and endosomal signaling. Sorting nexin 12 (SNX12) is one of the SNXs family members; however, its function remains unknown. To clarify the function of SNX12, in this study, we first investigated the expression profiles in mice, particularly in the central nervous system (CNS), and then analyzed the functional role on neurite outgrowth. We found that SNX12 was widely expressed in the adult mouse CNS and that its expression level was higher in the cerebral cortex than in other examined regions. SNX12 expression was detected in the neurons but not the glial cells of the adult mouse cerebral cortex. In the fetal brain, SNX12 expression increased during the embryonic stage and gradually decreased after birth. Although the immunoreactivities of SNX12 were widespread in the cerebral cortical cells in the fetal brain, the immunopositive signals of SNX12 were more intense in the postmitotic neurons in the cortical plate than in the proliferating precursor cells in the ventricular zone, suggesting that SNX12 plays critical roles in the postmitotic neurons during cerebral cortical development. Furthermore, in mouse neuroblastoma and N1E-115 cells and rat primary cortical neurons, SNX12 expression was increased as neurite outgrowth progressed and the knockdown of SNX12 attenuated the outgrowth of neurites. These results suggest that SNX12 regulates neurite formation during cerebral cortical development.