The progenitor cells of the embryonic telencephalon and the neonatal anterior subventricular zone differentially regulate their cell cycle

Abstract

For the last 10 years our laboratory has been studying the proliferation, migration and differentiation of neuronal progenitor cells located in the anterior part of the postnatal forebrain subventricular zone (SVZa). SVZa-derived cells possess a number of proliferative characteristics that distinguish them from the other progenitor cells in the central nervous system. This review summarizes our recent findings, in which we compared the pattern of cell cycle inhibitory proteins expressed by the neonatal SVZa to that of telencephalic ventricular zone cells.

Figure 1. Summary diagram depicting the subcellular changes of p19^INK4d expression by VZ cells compared to SVZa cells as they migrate to their final destinations

(A) Sagittal view of the embryonic telencephalon illustrating the laminar subdivisions of the developing cerebral cortex. Immature neurons of the VZ migrate through the layers of the telencephalon to reach the CP, where they complete their differentiation. (B) Sagittal view of the neonatal forebrain illustrating the migratory path of the SVZa-derived cells. The neurons that arise in the SVZa (solid black circle) migrate along the RMS to reach the olfactory bulb, where they differentiate into interneurons. The set of open arrowheads demarcates the border between the neurogenic SVZa and gliogenic posterior portion of the SVZ. The set of closed arrowheads indicates the caudal border of the main olfactory bulb. (C) Expression of p19^INK4d during the generation of a typical cortical neuron of the embryonic telencephalon. After VZ progenitor cells divide and withdraw from the mitotic cycle at the ventricular surface (a), the postmitotic progeny starts expressing p19^INK4d (black) at the cytoplasmic-nuclear border in the VZl (b). p19^INK4d expression is downregulated as the migrating neurons pass through the VZu (c) and is re-expressed in a punctate manner upon entering the IZ (d). Furthermore, within the CP, the p19^INK4d expression persists in the differentiating neurons (e–g) in a more diffuse manner with a perinuclear crescent shaped pattern. Gray shading represents expression of neuron-specific markers (Menezes and Luskin, 1994). (D) Expression of p19^INK4d during the generation of a typical interneuron of the neonatal olfactory bulb. Unlike the cells of the telencephalic VZ, the SVZa progenitor cells and their progeny are immunoreactive for the neuron-specific antibody TuJ1 (gray shading) at virtually all times in the RMS (h–l). The SVZa neuronal progenitor cells exhibit only negligible amounts of p19^INK4d in the SVZa (h). However, when in the proximal portion of the RMS, the TuJ1(+) SVZa-derived cells start to express p19^INK4d at their apical pole while en route to the olfactory bulb (i). Subsequently, SVZa-derived cell downregulate their expression of p19^INK4d and re-enter the cell cycle to undergo another round of cell division in the RMS (j). When in the olfactory bulb, the SVZa-derived cells terminally exit the cell cycle and migrate into one of the overlying cellular layers of the olfactory bulb. The p19^INK4d persists in the postmitotic olfactory bulb interneurons within the gcl and gl (k and l). AOB, accessory olfactory bulb; CC, corpus callosum; CP, cortical plate; CTX, cerebral cortex; epl, external plexiform layer; gcl, granule cell layer; gl, glomerular layer; hl, horizontal limb of the RMS; IZ, intermediate zone; LV, lateral ventricle; mcl, mitral cell layer; MZ, marginal zone; OB, olfactory bulb; RMS, rostral migratory stream; onl, olfactory nerve layer; sez, subependymal zone; SP, subplate; SVZa, anterior part of the neonatal subventricular zone; vl, vertical limb of RMS; VZ, ventricular zone; VZl, lower portion of the ventricular zone; VZu, upper portion of the ventricular zone.