Consequences of neural cell adhesion molecule deficiency on cell migrationin the rostral migratory stream of the mouse

In vertebrates, interneurons of the olfactory bulb (OB) are generated postn atally and throughout life at the subventricular zone of the forebrain. The neuronal precursors migrate tangentially through the forebrain using a wel l defined pathway, the rostral migratory stream (RMS), and a particular mod e of migration in a chain-like organization. A severe size reduction of the OB represents the most striking morphological phenotype in neural cell adh esion molecule (NCAM)-deficient mice. This defect has been traced back to a migration deficit of the precursors in the RMS and linked to the lack of t he polysialylated form of NCAM. In this study we investigate the morphologi cal alterations and functional properties of the RMS in mice totally devoid of all isoforms of NCAM and polysialic acid (PSA). We show that a morpholo gically altered, but defined and continuous pathway exists in mutants, and we present in vivo and in vitro evidence that PSA-NCAM in the RMS is not es sential for the formation and migration of chains. Instead, we find a massi ve gliosis associated with the formation of membrane specializations in a h eterotypic manner, linking precursors to astrocytes. This finding and the o ver-representation and defasciculation of axons in the pathway suggest that important interactions between migrating cells and their stationary enviro nment are perturbed in the mutants. Finally, we used transplantation experi ments to demonstrate that lack of PSA-NCAM leads to a decrease but not a to tal blockade of migration and demonstrate that the mutant RMS is functional in transporting normal neuronal precursors to the OB.