The factors affecting normal oligodendrocyte positioning in the cerebral cortex are unknown. Apart from the white matter, the highest numbers of oligodendrocytes in the rodent cortex are found in Layers V/VI, where the infragranular neurons normally reside. Few, if any, oligodendrocytes are normally found in the superficial cortical layers. To test whether or not this asymmetric positioning of oligodendrocytes is linked to the lamina positions of Layer V/VI projection neurons, mutant mice that cause neuronal layer inversion were examined. In three lines of mutant mice (Reeler, disabled-1, and p35) examined, representing two different genetic signaling pathways, the oligodendrocyte distribution was altered from an asymmetric to a symmetric distribution pattern. Unlike cortical neurons that are inverted in these mutant mice, the lack of oligodendrocyte inversion suggests a decoupling of the genetic mechanisms governing neuronal versus oligodendrocyte patterning. We conclude that oligodendrocyte positioning is not linked to the layer positions of V/VI projection neurons