From radial glia to pyramidal-projection neuron: transcription factor cascades in cerebral cortex development

Pyramidal-projection neurons are glutamatergic neurons that develop from progenitors in the ventricular and subventricular zones of the embryonic cortex. Recently, much has been learned about the cortical progenitor cells and the cellular and molecular mechanisms by which they produce projection neurons. We now know that radial glia are the progenitors of most or all projection neurons and that they generate neurons by two distinct mitotic sequences: direct neurogenesis to produce a single daughter neuron or indirect neurogenesis to produce two to four neurons via intermediate progenitor cells. The underlying genetic programs for proliferation and differentiation are controlled and implemented by specific transcription factors, whose interactions largely determine the cortical surface area, thickness, and neuronal subtype composition. In turn, transcription factor expression is modulated by extrinsic signals from patterning centers and adjacent cells and by intrinsic signals distributed asymmetrically within progenitors and daughter cells. Together, the new findings provide a coherent framework for understanding cortical neurogenesis.