N-CAM MUTATION INHIBITS TANGENTIAL NEURONAL MIGRATION AND IS PHENOCOPIED BY ENZYMATIC REMOVAL OF POLYSIALIC ACID

The mutation of N-CAM in mice produces a phenotype dominated by an und ersized olfactory bulb and accumulation of precursors in the subependy mal layer. We demonstrate here that this defect can be duplicated by i njection of an enzyme that specifically destroys the polysialic acid ( PSA) moiety associated with N-CAM. Studies of BrdU-labeled and pyknoti c cells suggest that this defect reflects a decrease in the rostral mi gration of olfactory precursors and not a change in the proliferation or rate of death of these cells. In addition to their ectopic location , these cells had fewer growth cone-like processes oriented along the migration route. In contrast to tangential movement, radial migration of granule cells in the olfactory bulb was not affected by loss of PSA . These results support the proposed role for PSA in cell translocatio n, discriminate between different mechanisms of cell migration, and pr ovide insight as to the nature of the N-CAM mutant phenotype.