The expression pattern of the cell cycle inhibitor p19INK4d by progenitor cells of the rat embryonic telencephalon and neonatal anterior subventricular zone

In this study we investigated whether the pattern of expression of the cyclin-dependent kinase inhibitor p19(INK4d) by the unique progenitor cells of the neonatal anterior subventricular zone (SVZa) can account for their ability to divide even though they express phenotypic characteristics of differentiated neurons. p19(INK4d) was chosen for analysis because it usually acts to block permanently the cell cycle at the G(1) phase. p19(INK4d) immunoreactivity and the incorporation of bromodeoxyuridine (BrdU) by SVZa cells were compared with that of the more typical progenitor cells of the prenatal telencephalic ventricular zone. In the developing telencephalon, p19(INK4d) is expressed by postmitotic cells and has a characteristic perinuclear distribution depending on the laminar position and state of differentiation of a cell. Moreover, the laminar-specific staining of the developing cerebral cortex revealed that the ventricular zone (VZ) is divided into p19(INK4d) (+) and p19(INK4d) (-) sublaminae, indicating that the VZ has a previously unrecognized level of functional organization. Furthermore, the rostral migratory stream, traversed by the SVZa-derived cells, exhibits an anterior (high)-posterior(low) gradient of p19(INK4d) expression. On the basis of the p19(INK4d) immunoreactivity and BrdU incorporation, SVZa-derived cells appear to exit and reenter the cell cycle successively. Thus, in contrast to telencephalic VZ cells, SVZa cells continue to undergo multiple rounds of division and differentiation before becoming postmitotic.