Transcriptional mechanisms of EphA7 gene expression in the developing cerebral cortex

The patterning of cortical areas is controlled by a combination of intrinsic factors that are expressed in the cortex and external signals such as inputs from the thalamus. EphA7 is a guidance receptor that is involved in key aspects of cortical development and is expressed in gradients within developing cortical areas. Here, we identified a regulatory element of the EphA7 promoter, named pA7, that can recapitulate salient features of the pattern of expression of EphA7, including cortical gradients. Using a pA7-Green fluorescent Protein (GFP) mouse reporter line, we isolated cortical neuron populations displaying different levels of EphA7/GFP expression. Transcriptome analysis of these populations enabled to identify many differentially expressed genes, including 26 transcription factors with putative binding sites in the pA7 element. Among these, Pbx1 was found to bind directly to the EphA7 promoter in the developing cortex. All genes validated further were confirmed to be expressed differentially in the developing cortex, similarly to EphA7. Their expression was unchanged in mutant mice defective for thalamocortical projections, indicating a transcriptional control largely intrinsic to the cortex. Our study identifies a novel repertoire of cortical neuron genes that may act upstream of, or together with EphA7, to control the patterning of cortical areas.