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Previous Article | Next Article
The Journal of Neuroscience, February 15, 2000, 20(4):1446-1457
Consequences of Neural Cell Adhesion Molecule Deficiency on Cell Migration in the Rostral Migratory Stream of the Mouse
Geneviève Chazal1, Pascale Durbec1, Aleksandar Jankovski2, Geneviève Rougon1, and Harold Cremer1 1 Laboratoire de Génétique et Physiologie du Développement, Institut de Biologie du Développement de Marseille, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale (INSERM)/Université de la Méditerranée, Campus de Luminy, 13288 Marseille, France, and 2 INSERM, Hôpital de la Salpétrière, 75651 Paris Cedex 13, France
In vertebrates, interneurons of the olfactory bulb (OB) are generated postnatally and throughout life at the subventricular zone of the forebrain. The neuronal precursors migrate tangentially through the forebrain using a well defined pathway, the rostral migratory stream (RMS), and a particular mode of migration in a chain-like organization. A severe size reduction of the OB represents the most striking morphological phenotype in neural cell adhesion 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 the polysialylated form of NCAM. In this study we investigate the morphological alterations and functional properties of the RMS in mice totally devoid of all isoforms of NCAM and polysialic acid (PSA). We show that a morphologically 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 essential for the formation and migration of chains. Instead, we find a massive gliosis associated with the formation of membrane specializations in a heterotypic manner, linking precursors to astrocytes. This finding and the over-representation and defasciculation of axons in the pathway suggest that important interactions between migrating cells and their stationary environment are perturbed in the mutants. Finally, we used transplantation experiments to demonstrate that lack of PSA-NCAM leads to a decrease but not a total blockade of migration and demonstrate that the mutant RMS is functional in transporting normal neuronal precursors to the OB.
Key words: cell adhesion molecules; subventricular zone; olfactory bulb; neurogenesis; tangential cell migration; polysialic acid
Copyright © 2000 Society for Neuroscience 0270-6474/00/2041446-12$05.00/0
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