The fates of cells generated at the end of neurogenesis in developing mouse cortex.

Abstract

Most cerebral cortical neurons are generated between embryonic days 11 and 17 (E11-17) in the mouse. Radial glial cells also proliferate during this time; they can give rise to neurons and many later transform into astrocytes. It is thought that most glial cells comprising the mature cortex, including additional astrocytes, are generated after neurogenesis is complete. Little is known about the cellular events that occur during the transition from the phase dominated by neurogenesis to that of gliogenesis. We labeled cells generated on E18 and E19 and the day of birth (P0) with bromodeoxyuridine and followed their fates over the following 20 days. Our results showed that, on E18-P0, cells divide throughout the ventricular zone, subventricular zone, intermediate zone, and to a lesser extent, the developing cortical plate, whereas neuronal precursors generated prior to E18 divide in the ventricular zone. Our results indicated that 30-40% of cells dividing on E18 give rise to neurons that migrate to the most superficial part of the cortex. The rest of the cells dividing on E18 and 76-94% of cells generated on E19 and P0 express the QKI RNA-binding protein, indicating that they either remain as multipotential progenitors or develop into glial cells. Nine to fifteen percent of cells generated on E18-P0 become glial fibrillary acidic protein-positive astrocytes. Many E19 and P0 labeled cells disappear between 2 and 20 days postlabeling, probably because they continue to divide. We conclude that the population of cells produced at the end of cortical neurogenesis is heterogeneous and comprises postmitotic neurons, glia (including astrocytes), and possibly multipotential progenitors.