Follow-up study of subventricular zone progenitors with multiple rounds of cell division during sulcogyrogenesis in the ferret cerebral cortex

摘要

The subventricular zone (SVZ) of the developing cerebral cortex appears transiently during cortical neurogenesis and is known as the second proliferative zone that contains intermediate progenitor cells and self-renewable neuronal stem cells—the so-called basal radial glia (bRG). The present study attempted to track the differentiation and migration dynamics of SVZ progenitors undergoing multiple cell divisions at the late stage of neurogenesis in a course of sulcogyrogenesis in the ferret, a gyrencephalic mammal. Ferret pups were given a 5-ethynyl-2′-deoxyuridine (EdU) injection on postnatal day (PD) 5 followed by a 5-bromo-2′-deoxyuridine (BrdU) injection on PD 7. The 48 h interval between EdU and BrdU injections covered the minimum times for the first and second S-phase of self-renewing bRG. Two h after BrdU injection, EdU/BrdU-double labeled cells were found in the inner or outer SVZ (iSVZ and oSVZ), more than 80% of which were Sox2-positive. Furthermore, 95.8% of EdU/BrdU-double labeled Sox2-positive progenitors in the iSVZ and 84.2% in the oSVZ were also Pax6-positive, defining these progenitors as bRG. On PD 20, all EdU/BrdU-double labeled cells were NeuN-immunopositive, and more than 60% of these were parvalbumin-immunopositive. EdU/BrdU-double labeled neurons were distributed densely in the superficial portion of the outer cortical stratum. Cluster analysis divided the gyral and sulcal regions into higher and lower density groups, respectively, based on the diversity of the cortical density of EdU/BrdU-double labeled neurons. The higher density group included the gyral and sulcal regions of the prefrontal, parietooccipital and/or cingulate cortex, corresponding to cortical regions associated with evolutionary expansion. Although a limited population of neurons within a narrow time window of cortical neurogenesis was tracked, the present findings suggest that neurons derived from bRG at the late stage of neurogenesis express parvalbumin during corticohistogenesis. Due to the diversity of sulcogyral distributions, neurons derived from bRG may be implicated in evolutionary cortical expansion.