Disrupted cortical map and absence of cortical barrels in growth-associated protein (GAP)-43 knockout mice

There is strong evidence that growth-associated protein (GAP-43), a protein found only in the nervous system, regulates the response of neurons to axo nal guidance signals. However, its role in complex spatial patterning in ce rebral cortex has not been explored. We show that mice lacking GAP-43 expre ssion (-/-) fail to establish the ordered whisker representation (barrel ar ray) normally found in layer IV of rodent primary somatosensory cortex. Tha lamocortical afferents to -/- cortex form irregular patches in layer IV wit hin a poorly defined cortical field, which varies between hemispheres, rath er than the stereotypic, whisker-specific, segregated map seen in normal an imals. Furthermore, many thalamocortical afferents project abnormally to wi dely separated cortical targets. Taken together, our findings indicate a lo ss of identifiable whisker territories in the GAP-43 -/- mouse cortex, Here , we present a disrupted somatotopic map phenotype in cortex, in clear cont rast to the blurring of boundaries within an ordered whisker map in other b arrelless mutants. Our results indicate that GAP-43 expression is critical for the normal establishment of ordered topography in barrel cortex.