Identification of ventricular‐side‐enriched molecules regulated in a stage‐dependent manner during cerebral cortical development

Radial glial cells are the main component of the embryonic cortical ventricular zone (VZ), producing deep‐layer excitatory neurons in the early stage and upper‐layer excitatory neurons in the late stage of development. Previous studies have suggested that the laminar fate of deep‐layer neurons might be determined by early‐stage‐specific secretory or transmembrane molecules (S/TMs) in the VZ. However, the different properties required to produce the different types of neurons in early‐stage and late‐stage VZ cells are largely unknown. Herein, we investigated the stage‐dependent transcriptional profiles of the ventricular side of the mouse cortex, which was manually dissected at embryonic day (E)12, E14 and E16, and identified 3985 ‘VZ‐enriched’ genes, regulated stage‐dependently, by GeneChip analysis. These molecules were classified into nine types based on stage‐dependent regulation patterns. Prediction programs for the S/TMs revealed 659 ‘VZ‐enriched’ S/TMs. In situ hybridization and real‐time PCR analysis for several of these molecules showed results consistent with the statistical analysis of the GeneChip experiments. Moreover, we identified 17 cell cycle‐related early‐stage and ‘VZ‐enriched’ molecules. These molecules included not only those involved in cell cycle progression, but also essential molecules for DNA double‐strand break repair, such as Rad51 and Rpa1. These results suggest that the early stage‐VZ cells, which produce both deep‐ and upper‐layer neurons, and the late‐stage VZ cells, which produce only upper‐layer neurons, are intrinsically different. The gene lists presented here will be useful for the investigation of stage‐dependent changes in VZ cells and their regulatory mechanisms in the developing cortex.