Objetivo Our objectives were - to characterize the structure, the function and the regulation of expression of adhesion molecules and - pinpoint their involvement in the ontogeny and regenerative processes of the mammalian nervous system.PSA-NCAM, a unique permissive element for cell plasticity is involved in cell migration and required for activity-induced synaptic plasticity. Mechanisms controlling its expression have been discovered. Cell surface expression of adhesion molecules is under the control of neuronal activity, this observation provides a new framework for understanding activity-dependent reorganisation of synaptic networks. Growth factors up-regulate the expression of adhesion molecules in cultured Schawnn cells. Cell surface metallo-proteases play a role in peripheral nerve development and regeneration after injury. Activation of glycosyl-phosphatidylinositol anchored neuronal adhesion molecules leads to triggering of intracellular second messenger pathways. Effects of inhibitory molecules on axonal regeneration of CNS and PNS neurons depends on their developmental stage.MAJOR SCIENTIFIC BREAKTROUGHS:Laboratory 1 has chosen to work on the NCAM and F3 adhesion molecules of the immunoglobulin super-family which are known to play a role in axonal growth during development. Together with laboratory 4 they have shown, using post-hypophysial tissue explants as a model, that PSA-NCAM is necessary for the migration of oligodendrocyte progenitor cells, a population of cells particularly motile in vivo, and that PSA expression is controlled by NMDA receptor activation. They have also shown that PSA-NCAM is required for activity-induced synaptic plasticity and that it can be externalized on the cell surface of neurons by regulated exocytosis. Laboratory 2, in collaboration with laboratory 3, has shown that endopeptidase-24.11 is normally present at high levels in all neonatal and early postnatal Schwann cells and is gradually suppressed while myelinisation proceeds. This enzyme is re-expressed with the same time-course as NGF receptors after axotomy suggesting it might play a role in axonal regeneration. Laboratory 3 has mainly focused on the characterization and fate of Schwann cell precursors. It has also investigated the expression of molecules characterized by laboratories 1 and 2 on these precursors. The BM88 molecule recently cloned by laboratory 2 is expressed on both precursors and Schwann cells, so it will not be possible to consider it, as previously hoped, as a marker for the transition of the precursors to Schwann cells. Laboratories 1 and 2 have started a collaboration to investigate the possibility of using cerebellar tissue explants for retroviral infections aimed at testing the in vivo function of adhesion molecules. Laboratories 5 and 1 showed, using transfected cells as a model, that mimicking F3 triggering by cross-linking with antibodies induced the phosphorylation of intracellular substrates. In addition, they were able to co-immunoprecipitate a tyrosine kinase activity associated with F3 both in aggregated transfected cells and cerebellar neurons, reinforcing the observation that tyrosine kinases are involved in signalling following F3-mediated adhesion. Laboratory 6 has carried out experiments to decipher the function of the P31 (mCD24) adhesion molecule. Using P31 expressing glial cells, engineered by laboratory 1, it has shown that such cells used as a substrate monolayer prevented neurite regeneration of postnatal and adult sensory neurons and retinal ganglion cells but not neurite outgrowth of embryonic neurons. Neurons from a P31 knock-out mouse were also used. Taken together the data indicate that mature neurons expressed a receptor for P31 whose activation leads to inhibition of axonal growth. Ámbito científico natural sciencesbiological sciencesneurobiologymedical and health sciencesclinical medicineobstetricspostnatal carenatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programa(s) FP3-BIOTECH 1 - Specific research and technological development programme (EEC) in the field of biotechnology, 1990-1994 Tema(s) 2.3 - Communication systems within living matter Convocatoria de propuestas Data not available Régimen de financiación CON - Coordination of research actions Coordinador Université d'Aix-Marseille II Aportación de la UE Sin datos Dirección 70 route Léon Lachamp 13288 Marseille Francia Ver en el mapa Coste total Sin datos Participantes (5) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo Consiglio Nazionale delle Ricerche (CNR) Italia Aportación de la UE Sin datos Dirección Via Archirafi 20 90123 Palermo Ver en el mapa Coste total Sin datos HELLENIC PASTEUR INSTITUTE Grecia Aportación de la UE Sin datos Dirección VASSILISSIS SOFIAS AVENUE 127 11521 ATHENS Ver en el mapa Coste total Sin datos UNIVERSITE DE GENEVE Suiza Aportación de la UE Sin datos Dirección PLACE DE L'UNIVERSITE 3 1211 GENEVE 4 Ver en el mapa Coste total Sin datos UNIVERSITY COLLEGE LONDON Reino Unido Aportación de la UE Sin datos Dirección Gower Street LONDON Ver en el mapa Enlaces Sitio web Opens in new window Coste total Sin datos United Medical and Dental Schools of Guy's and St.Thomas's Hospitals Reino Unido Aportación de la UE Sin datos Dirección Lambeth Palace Road SE1 7EH London Ver en el mapa Coste total Sin datos
