Removal of polysialic acid triggers dispersion of subventricularly derived neuroblasts into surrounding CNS tissues.
Cells generated in the subventricular zone give rise to neuroblasts that migrate to the olfactory bulb (OB) along the rostral migratory stream (RMS). The polysialylated form of neural cell adhesion molecule (PSA-NCAM) is expressed by these cells, and has been shown to both promote their migration and suppress differentiation induced by NCAM. In the present study, enzymatic removal of PSA from these neuroblasts using PSA-specific endoneuraminidase has been found not only to disrupt the tangential migration and cellular organization of the RMS, but also to cause a massive dispersion of BrdU (5-bromo-2'-deoxyuridine)-labeled neuroblasts into surrounding brain regions, including cortex and striatum. These dispersed cells are capable of differentiation, some into mature neurons, and could potentially be of value in the repair of CNS injury. Although the removal of PSA by genetic deletion of NCAM also results in a smaller OB and a swollen RMS, the cells do not escape the RMS in large numbers. These findings suggest that the presence of NCAM without PSA plays a role in the dispersion process, possibly by inducing a new pattern of migration associated with NCAM-dependent differentiation.
Laboratory of Cellular and Developmental Neuroscience, Department of Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Daniela
D
Battista
Urs
U
Rutishauser
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002552:Cerebral Ventricles / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D006026:Glycoside Hydrolases / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D012794:Sialic Acids / Q000172:deficiency*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*
D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; C021319:polysialic acid; D006026:Glycoside Hydrolases; C090534:endo-alpha-sialidase; D001973:Bromodeoxyuridine