Cortical Ventricular Zone Progenitors and Their Progeny Maintain Spatial Relationships and Radial Patterning during Preplate Development Indicating an Early Protomap

Abstract

The graded expression of transcription factors by progenitors in the ventricular zone (VZ) confers positional or area identity that is inherited by subplate (SP) neurons and governs their expression of guidance molecules for thalamocortical axons and other properties required for cortical area specification. This mechanism would be most efficient if VZ progenitors and their SP neuronal progeny maintain neighbor relationships during the generation of the preplate (PP), the precursor of the SP. Therefore, a major goal of this study is to determine whether progenitors in the cortical VZ and their progeny maintain neighbor relationships during the genesis of the neocortical PP. We used time-lapse video microscopy to follow the movements of VZ progenitors and the radial movement of their progeny and distribution in the PP in whole-mount or slice cortical explants from embryonic rats at stages when PP neurons are generated. We show that labeled VZ cells proliferate and have a strong tendency to retain neighbor relationships within the VZ and that their neuronal progeny move superficially along a radial column to form the overlying PP; during this process, their neuronal progeny also retain neighbor relationships and thereby form the PP in spatial register with the VZ progenitors that generate them. This behavior differs from that reported at later stages of cortical development, when cortical plate (CP) neurons are generated, and considerable dispersion is evident among both cells within the VZ and neuronal progeny as they migrate from the VZ to the CP. However, our findings show that at the early stage of cortical development, when PP/SP neurons are generated, the VZ is, at a cellular level, a "protomap" of the PP/SP.