The contribution of extrinsic and genetic mechanisms in determining areas o
f the mammalian neocortex has been a contested issue. This study analyzes t
he roles of the regulatory genes Emx2 and Pax6, which are expressed in oppo
sing gradients in the neocortical ventricular zone, in specifying areas. Ch
anges in the patterning of molecular markers and area-specific connections
between the colter and thalamus suggest that arealization of the neocortex
is disproportionately altered in Emx2 and Pax6 mutant mice in opposing mann
ers predicted from their countergradients of expression: rostral areas expa
nd and caudal areas contract in Emx2 mutants, whereas the opposite effect i
s seen in Pax6 mutants. These findings suggest that Emx2 and Pax6 cooperate
to regulate arealization of the neocortex and to confer area identity to c
ortical cells.