The cell biology of neurogenesis

Abstract

Neurons in the rodent central nervous system originate from three classes of neural stem and progenitor cells — neuroepithelial cells, radial glial cells and basal progenitors. These cells undergo three main types of division — symmetric, proliferative division (neuroepithelial cells); asymmetric, neurogenic division (neuroepithelial cells and radial glial cells); and symmetric, neurogenic division (radial glial cells and basal progenitors). With the onset of neurogenesis, neuroepithelial cells transform into radial glial cells. Both neuroepithelial and radial glial cells are characterized by apical–basal polarity and interkinetic nuclear migration. The orientation of the cleavage plane relative to the apical–basal axis of neuroepithelial and radial glial cells is an important determinant of the type of division. Most neurogenic divisions of neuroepithelial and radial glial cells in the embryonic mouse brain involve a vertical cleavage plane (parallel to the apical–basal axis), which can either bisect the apical plasma membrane to result in a symmetric, proliferative division, or bypass the apical plasma membrane to result in an asymmetric, neurogenic division. Interkinetic nuclear migration is a hallmark of neuroepithelial and radial glial cells, but its physiological significance is poorly understood. The cellular machinery that underlies this process seems to involve both microtubules and the actin cytoskeleton. Concomitant with the onset and progression of neurogenesis, the length of the cell cycle of neuroepithelial and radial glial cells increases. Neuroepithelial cells that undergo neurogenic divisions have a longer cell cycle than those that undergo proliferative divisions. Moreover, in support of the cell-cycle length hypothesis, lengthening the cell cycle of neuroepithelial cells can be sufficient to switch neuroepithelial cells from proliferative to neurogenic divisions. These insights into the spatial and temporal control mechanisms that operate in neural stem and progenitor cells during embryonic neurogenesis probably have implications for adult neural stem cells and adult neurogenesis.