Letter to Neuroscience Letter to Neuroscience NR-CAM AND TAG-1 ARE EXPRESSED IN DISTINCT POPULATIONS OF DEVELOPING PRECEREBELLAR AND CEREBELLAR NEURONS S. BACKER, a T. SAKURAI, b M. GRUMET, c C. SOTELO a and E. BLOCH-GALLEGO aà a INSERM U106, Ho “pital de la Salpe “trie 're, 75013 Paris, France b Mount Sinai School of Medicine, Department of Biochemistry and Molecular Biology and Neurology, New York, NY 10029, USA c W.M. Keck Center for Collaborative Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ 08854-8082, USA Key words: adhesion molecules, £oor-plate, inferior olivary, lateral reticular and pontine nuclei, cerebellum, development, mouse embryo and postnatal, migration. Nr-CAM and TAG-1 interact at the £oor-plate during the formation of spinal cord commissural projections [Stoeckli, E.T., Landmesser, L.T., Sci. 274 (1995) 1123-1133; Fitzli, D., Stoeckli, E.T., Kunz, S., Siribour, K., Rader, C., Kunz, B., Kozlov, S.V., Buchstaller, A., Lane, R.P., Suter, D.M., Dreyer, W.J., Sonderegger, P., J. Cell. Biol. 149 (2000) 951-968]. We report here the spatio-tem- poral patterns of expression of these two adhesion mole- cules during the development of the lower brainstem (medulla and pons) and cerebellum. Nr-CAM and Tag-1 label distinct populations of precerebellar neurons at key steps of their development. Nr-CAM expression starts at E11.5^E12 in the £oor-plate, that constitutes an intermedi- ate target during axon outgrowth and nuclear migration of precerebellar neurons. At E13^E14, it is expressed in both £oor-plate and inferior olivary nuclei (ION) neurons before being strictly restricted to ION neurons from E15 onwards. Furthermore Nr-CAM, which is widely expressed in the cerebellum during embryonic development, becomes strictly con¢ned to Purkinje and Golgi cells in postnatal cerebellum, suggesting a possible role of Nr-CAM for the maturation or stabilization of the synaptic contacts, in particular between climbing ¢bers and Purkinje cells. On the other hand, Tag-1 is expressed by migrating neurons that will form the lateral reticular and basilar pontine nuclei. These results emphasize the possibility that TAG- 1/Nr-CAM interactions are also involved in the develop- ment of the cerebellar system (precerebellar and cerebellar neurons). However, the pattern of cerebellar expression of TAG-1 ^ early migrating Purkinje cells up to E14 and external granular cells ^ prevents the implication of this adhesion molecule in the organization of extracerebellar projections. ß 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved. Precerebellar neurons follow a circumferential migration from the alar plate of the rhombencephalon, the caudal rhombic lip (Altman and Bayer, 1987a,b) to their ¢nal destinations in the basilar pons (PN), the external cunea- tus, the lateral reticular (LRN) and the inferior olivary nuclei (ION). During this process, the cell nuclei of ION and PN neurons translocate within their axons until they reach the £oor-plate where they stop, while their axons have already crossed the midline to project to the con- tralateral cerebellum. Whereas cell bodies of LRN neu- rons cross the £oor-plate and stop contralaterally to their generation site (Bourrat and Sotelo, 1988). Thus, the £oor-plate is an essential intermediate target in the migration of precerebellar neurons and the development of their cerebellar projections. In agreement with this proposition, netrin-1, a chemotropic factor which is strongly expressed by the £oor-plate, is involved in the proper migration of precerebellar neurons, in particular ION, LRN and PN (Bloch-Gallego et al., 1999; Yee et al., 1999; Alcantara et al., 2000). In addition to chemo- tropic cues, growing axons and migrating neurons can also be oriented by contact cues, particularly adhe- sion molecules (Tessier-Lavigne and Goodman, 1996; Rutishauser, 2000). Such kind of contact mechanisms, also involving the £oor-plate, have been reported in the spinal cord. An interaction of growth cone axonin-1/ TAG-1 with the £oor-plate NgCAM-related cell adhe- sion molecule (Nr-CAM) was shown to play a crucial role in commissural axon guidance across the midline of the spinal cord in both chick (Stoeckli and Landmesser, 1995) and mouse (Lustig et al., 1999). This direct inter- action of TAG-1 with Nr-CAM results in guidance, but not promotion of growth of commissural axons (Fitzli et al., 2000). In the brainstem, the growth cones of the 743 *Corresponding author. Tel.: +33-1-42-16-26-81; fax: +33-1-45-70- 99-90. E-mail address : gallego@infobiogen.fr (E. Bloch-Gallego). NSC 5664 5-8-02 www.neuroscience-ibro.com Neuroscience Vol. 113, No. 4, pp. 743^748, 2002 ß 2002 IBRO. Published by Elsevier Science Ltd All rights reserved. Printed in Great Britain PII:S0306-4522(02)00221-X 0306-4522/02 $22.00+0.00