Co-regulated gene expression downstream of a single transcription factor controls the acquisition of corticospinal motor neuron identity

The neocortex contains an unparalleled diversity of neuronal subtypes responsible for complex behavior. Each cortical neuron has distinct traits, which are developmentally acquired under the control of batteries of neuron subtype-specific and pan-neuronal genes. The cis-regulatory logic that orchestrates the coordinated regulation of each unique combination of genes is not known for any class of neurons of the neocortex. We report that Fezf2, a transcription factor able to induce defining features of corticospinal motor neurons (CSMN), associates with the proximal promoters and regulates expression of series of CSMN signature genes. Fezf2 targets are functionally relevant as demonstrated by the finding that Fezf2 governs expression of the axon guidance receptor EphB1 to execute the ipsilateral extension of the corticospinal tract. Our data indicate that co-regulated expression of neuron subtype-specific gene batteries by a common transcription factor is one component of the regulatory logic responsible for the establishment of CSMN identity. Fezf2 binding is characterized in neurospheres using ChIP-seq targeted against 3Flag-tagged Fezf2. Two types of control experiments were performed: mock IP and GFP-3Flag ChIP-seq. All experiments were performed in biological duplicate.