The mammalian cortex is highly sensitive to mutations that disrupt mitosis. During cortical development, neural stem cells (NSCs) in the dorsal telencephalon first divide symmetrically, amplifying the stem cell pool. They then transition to neural progenitor cells (NPCs), which divide asymmetrically to generate neuronal-fated cells (which themselves can later expand) while maintaining the progenitor pool. However, the molecular regulation of this switch from early expansive to late neurogenic mitosis is still poorly understood, and is the subject of Caroline Johnson and H. Troy Ghashghaei's new paper. The authors had previously shown that loss of the specificity protein 2 (Sp2) transcription factor slows down cortical mitosis, and now extend this work by taking advantage of the mosaic analysis with double markers (MADM) technique, which allows simultaneous fluorescent labelling and gene knockout in somatic cell clones. They find that dividing Sp2−/− NPCs take longer to adopt a rounded morphology and spend more time in prophase and prometaphase. Prolonged mitosis leads to an attenuated expansion of progenitor cells in the ventricular/sub-ventricular zone, and a reduced number of cells in upper cortical layers. In contrast to the situation in NPCs, loss of Sp2 does not affect the symmetric division or differentiation of NSCs in early corticogenesis. Thus, Sp2 is a stage-specific transcription factor required for NPC mitosis, demonstrating a distinct molecular regulation of early and late corticogenesis.
