Emx2 patterns the neocortex by regulating FGF positional signaling

Molecular genetic studies implicate fibroblast growth factor 8 (FGF8), and the transcription factor Emx2, in development of the neocortical area map. Both are proposed to specify area position along the anterior-to-posterior axis of the cortical primordium. Whether FGF8 and Emx2 act independently or coordinately, or whether one controls the other, has not been determined. Here we report that Emx2, by regulating FGF8, has an indirect but vital role in area-map development. Using electroporation-mediated gene transfer in living mouse embryos, we found that overexpressing Emx2 altered the area map, but only when ectopic Emx2 overlapped the FGF8 source. Furthermore, we found that FGF8 levels were decreased by excess Emx2, and increased in mice lacking Emx2. Finally, cortical domain shifts that characterize Emx2 mutants were rescued by sequestering excess FGF8 with a truncated FGF receptor construct. These findings begin to clarify the signaling network that patterns the neocortical area map.