A mapping label required for normal scale of body representation in the cortex

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The neocortical primary somatosensory area (S1) consists of a map of the body surface. The cortical area devoted to different regions, such as parts of the face or hands, reflects their functional importance. Here we investigated the role of genetically determined positional labels in neocortical mapping. Ephrin-A5 was expressed in a medial > lateral gradient across S1, whereas its receptor EphA4 was in a matching gradient across the thalamic ventrobasal (VB) complex, which provides S1 input. Ephrin-A5 had topographically specific effects on VB axon guidance in vitro. Ephrin-A5 gene disruption caused graded, topographically specific distortion in the S1 body map, with medial regions contracted and lateral regions expanded, changing relative areas up to 50% in developing and adult mice. These results provide evidence for within-area thalamocortical mapping labels and show that a genetic difference can cause a lasting change in relative scale of different regions within a topographic map.

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Figure 1: Ephrin-A5 RNA expression within motor and sensory areas of the developing rodent neocortex.
Figure 2: Ephrin-A5 graded expression across the developing rodent somatosensory cortex.
Figure 3: The VB complex, the main somatosensory relay to the cortex, displays graded Eph receptor expression, and its axons are differentially repelled by ephrin-A5 in vitro.
Figure 4: Connectivity and pattern of the thalamocortical somatosensory map are grossly normal in ephrin-A5−/− mice.
Figure 5: Expansions and contractions in the cortical somatosensory map of ephrin-A-5−/− mice.


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We thank David Feldheim, Michael Hansen, Verne Caviness, David Van Vactor, Rick Born, Gerard Dallal, Sonal Jhaveri, Clay Reid and Michael Belliveau for help and advice. This work was supported by grants from the US NIH and NSF, the Swedish MRC, the Klingenstein foundation, the NATO/Belgian-American Educational Foundation and the Belgian FNRS.

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Correspondence to John G. Flanagan.

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