Fgf8 regulates the development of intra-neocortical projections.

The process of generating functionally distinct neocortical areas requires the formation of an intra-neocortical connectivity map. Here, we explore the early development of murine intra-neocortical projections and find that axons from rostral and caudal neurons remain, respectively, within large rostral and caudal domains of the neonatal neocortex. Despite evidence that thalamic input can regulate neocortical areal properties, we found that the neonatal intra-neocortical projection pattern was not perturbed when thalamic input was absent in Gbx2 mutants. On the contrary, in Fgf8 hypomorphic mutants, the rostral neocortex of which acquires more caudal molecular properties, caudally located neurons ectopically project axons into the rostral cortex. Therefore, neocortical patterning by Fgf8 also contributes to arealization through mediating early development of intra-neocortical connectivity.