Polysialic acid facilitates migration of luteinizing hormone-releasing hormone neurons on vomeronasal axons

Luteinizing hormone-releasing hormone (LHRH) neurons migrate from the olfac tory placode to the forebrain in association with vomeronasal nerves (VNN) that express the polysialic acid-rich form of the neural cell adhesion mole cule (PSA-NCAM). Two approaches were used to investigate the role of PSA-NC AM: injection of mouse embryos with endoneuraminidase N, followed by the an alysis of LHRH cell positions, and examination of LHRH cell positions in mu tant mice deficient in the expression of NCAM or the NCAM-180 isoform, whic h carries nearly all PSA in the brain. The enzymatic removal of PSA at embr yonic day 12 significantly inhibited the migration of nearly half of the LH RH neuron population, without affecting the VNN tract itself. Surprisingly, the absence of NCAM or NCAM-180 did not produce this effect. However, a sh ift in the route of migration, resulting in an excess number of LHRH cells in the accessory olfactory bulb, was observed in the NCAM-180 mutant. Furth ermore, it was found that PSA expressed by the proximal VNN and its distal branch leading to the accessory bulb, but not the branch leading to the for ebrain, was associated with the NCAM-140 isoform and thus was retained in t he NCAM-180 mutant. These results provide two types of evidence that PSA-NC AM plays a role in LHRH cell migration: promotion of cell movement along th e VNN tract that is sensitive to acute (enzymatic), but not chronic (geneti c), removal of PSA-NCAM, and a preference of a subset of migrating LHRH cel ls for a PSA-positive axon branch over a PSA-negative branch in the NCAM-18 0 mutant.