Molecular and Morphological Heterogeneity of Neural Precursors in the Mouse Neocortical Proliferative Zones

Abstract

The proliferative ventricular zone (VZ) is the main source of projection neurons for the overlying cerebral neocortex. The number and diversity of neocortical neurons is determined, in part, by factors controlling the proliferation and specification of VZ cells during embryonic development. We used a variety of methods, including in utero electroporation with specific cellular markers, computer-assisted serial EM cell reconstruction, and time-lapse multiphoton imaging to characterize the molecular and morphological characteristics of the VZ constituents and to capture their behavior during cell division. Our analyses reveal at least two types of dividing cells in the VZ: (1) radial glial cells (RGCs) that span the entire neocortical wall and maintain contact both at the ventricular and pial surfaces throughout mitotic division, and (2) short neural precursors (SNPs) that possess a ventricular endfoot and a basal process of variable length that is retracted during mitotic division. These two precursor cell classes are present concomitantly in the VZ, but their relative number changes over the course of cortical neurogenesis. Moreover, the SNPs are morphologically, ultrastructurally and molecularly distinct from dividing RGCs. For example, SNPs are marked by their preferential expression of the tubulin α-1 promoter whereas RGCs instead express the glutamate–aspartate transporter and brain lipid binding protein promoters. In contrast to recent studies that suggest that RGCs are the sole type of VZ precursor, the present study indicates that the VZ in murine dorsal telencephalon is similar to that in human and nonhuman primates, because it contains multiple types of neuronal precursors.