Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells

Abstract

Mature neocortical layers all derive from the cortical plate (CP), a transient zone in the dorsal telencephalon into which young neurons are continuously delivered. To understand cytogenetic and histogenetic events that trigger the emergence of the CP, we have used a slice culture technique. Most divisions at the ventricular surface generated paired cycling daughters (P/P divisions) and the majority of the P/P divisions were asymmetric in daughter cell behavior; they frequently sent one daughter cell to a non-surface (NS)position, the subventricular zone (SVZ), within a single cell-cycle length while keeping the other mitotic daughter for division at the surface. The NS-dividing cells were mostly Hu+ and their daughters were also Hu+, suggesting their commitment to the neuronal lineage and supply of early neurons at a position much closer to their destiny than from the ventricular surface. The release of a cycling daughter cell to SVZ was achieved by collapse of the ventricular process of the cell, followed by its NS division. Neurogenin2 (Ngn2) was immunohistochemically detected in a certain cycling population during G1 phase and was further restricted during G2-M phases to the SVZ-directed population. Its retroviral introduction converted surface divisions to NS divisions. The asymmetric P/P division may therefore contribute to efficient neuron/progenitor segregation required for CP initiation through cell cycle-dependent and lineage-restricted expression of Ngn2.

The determination of projection neuron identity in the developing cerebral cortex

“…Direct evidence that the SVZ is a neurogenic zone has been derived from a recent series of elegant imaging experiments [19,20] in conjunction with related work from other labs [21][22][23]. Noctor and colleagues used time-lapse confocal time-lapse microscopy to track the behavior of individual GFP-labeled mitotic progenitors in the VZ and SVZ, and then to follow the behavior and fates of their daughter cells [19,24,25].…”

“…At mid-to late stages of neurogenesis, the outcomes of VZ cell divisions undergo a fundamental alteration. Although the cell divisions remain asymmetric, the daughter cell that exits the VZ does not differentiate directly into a neuron, but rather moves into the SVZ and undergoes one or more symmetric neurogenic divisions, thus serving as a transit amplifying cell [23][24][25]28]. It is these divisions that appear to be primarily responsible for generating the neurons that migrate into the upper layers.…”

Neuronal stem cells in the central nervous system and in human diseases

“…However, the types of cells undergoing mitosis are still unclear. Recent studies indicate that throughout most of neurogenesis, other than an active role in VZ, RG cells also divide to populate the embryonic SVZ (Haubensak et al, 2004;Miyata et al, 2004;Noctor et al, 2004Noctor et al, , 2007b. RG cells usually undergo asymmetric cell division to yield a new RG cell and a neuron or an intermediate neural progenitor cell (IPC) (Fig.…”

Emx2 and Foxg1 Inhibit Gliogenesis and Promote Neuronogenesis

“…Neuronal-restricted progenitors (NPs) include apical short neuronal precursors/''pin-like'' cells, within the VZ, and basal intermediate precursor cells, in both VZ and subventricular zone (SVZ). Bipotent glial-restricted progenitors (hereafter referred to as glial progenitors [GPs]) generate both astrocytes and oligodendrocytes [7][8][9][10][11][12][13][14][15].…”