The neocortical primary somatosensory area (S1) consists of a map of the bo
dy surface. The cortical area devoted to different regions, such as parts o
f the face or hands, reflects their functional importance. Here we investig
ated the role of genetically determined positional labels in neocortical ma
pping. Ephrin-A5 was expressed in a medial > lateral gradient across S1, wh
ereas its receptor EphA4 was in a matching gradient across the thalamic ven
trobasal (VB) complex, which provides S1 input. Ephrin-A5 had topographical
ly specific effects on VB axon guidance in vitro. Ephrin-A5 gene disruption
caused graded, topographically specific distortion in the S1 body map, wit
h medial regions contracted and lateral regions expanded, changing relative
areas up to 50% in developing and adult mice. These results provide eviden
ce for within-area thalamocortical mapping labels and show that a genetic d
ifference can cause a lasting change in relative scale of different regions
within a topographic map.