Aberrant axonal projections from mammillary bodies in Pax6 mutant mice: possible roles of Netrin-1 and Slit 2 in mammillary projections.

Early events in the axonal tract formation from mammillary bodies remain poorly understood. In the present study, we reported an aberrant pattern of axonal projections from mammillary bodies to the dorsal thalamus in mice lacking the transcription factor Pax6. We found that Netrin-1 was ectopically up-regulated and that both Slit1 and Slit2 were down-regulated in the presumptive dorsal thalamus of Pax6 mutant mice. We then examined the effects of Netrin-1 and Slit2 on the mammillary axons by in utero electroporation techniques. Netrin-1 had an attractive action toward the mammillary axons. Moreover, mammillary trajectories were disorganized in Netrin-1-deficient mice. On the other hand, Slit2 had a repulsive effect on the mammillary axons. These findings suggest that the combination of Netrin and Slit may be involved in proper axonal projection from the mammillary bodies and that their misexpression in the diencephalon may cause the misrouting of these axons in Pax6 mutant mice.