Assembling a neural circuit: cell fate determination during brain development

The cerebral cortex is patterned into layers, each of which contains neurons with similar morphologies and axonal connections. During early stages of development, neural progenitors in the cerebral cortex normally produce neurons of different layers during successive cell divisions. Early progenitor cells are multipotent with respect to the production of different laminar phenotypes, but this potential becomes progressively restricted over time during development. Fezl, a putative zinc‐finger transcriptional repressor, is required for the layer‐specific differentiation of projection neurons in cortical layer 5. The disruption of Fezl leads to molecular, morphological and axonal targeting defects in these neurons: the corticospinal tract was absent, and corticotectal and pontine projections were severely reduced. The expression of many molecular markers for deep layer neurons was either reduced or absent in the Fezl−/ − cerebral cortex. Most strikingly, Ctip2, a transcription factor required for the differentiation and/or axon targeting of corticospinal motor neurons, was not expressed in Fezl‐deficient cortical neurons. These results suggest that Fezl is an essential regulator of the layer 5 subcortical projection neuron fate.