Ectopically localized HNK-1 epitope perturbs migration of the midbrain neural crest cells in Pax6 mutant rat
Small eye rats, which have a mutation in a gene encoding transcription factor Pax6, exhibit impaired migration of the midbrain neural crest cells, thereby showing severe craniofacial defects. Orthotopic grafting of the midbrain neural crest cells taken from the wild-type into Pax6 mutant embryos has suggested environmental defects along the migratory pathway of the midbrain crest cells. In the present study we found that the HNK-1 carbohydrate epitope was ectopically localized in the frontonasal epithelium of Pax6 mutant embryos. The GlcAT-P gene, encoding an enzyme for the synthesis of the HNK-1 epitope, was also expressed ectopically in the frontonasal epithelium of the mutant. In explant cultures, the migration rate of neural crest cells from the midbrain, but not from the forebrain, was significantly less in HNK-1-coated dishes than in non-coated dishes. These results suggest that the arrested migration of the midbrain crest cells in Pax6 mutant embryos may, at least in part, be due to the inhibitory effect of the HNK-1 epitope ectopically localized in the frontonasal epithelium.