During development of the neocortex, many diverse projection neuron subtypes are generated under regulation of cell-extrinsic and cell-intrinsic controls. One broad projection neuron class, corticofugal projection neurons (CFuPN), is the primary output neuron population of the neocortex. CFuPN axons innervate sub-cortical targets including thalamus, striatum, brainstem, and spinal cord.
By assessing multiple positive and negative markers of forebrain progenitors and neurons, the authors show that now-standard, partially directed neocortical differentiation of mouse embryonic stem cells generates neurons that most closely resemble neocortical projection neurons during mid-corticogenesis. These neurons are“stalled” in subtype-specific molecular refinements, as compared to primary, dissociated E15.5 neocortical neurons cultured under the same in vitro conditions.
