Objective To define when and where the oligodendrocyte lineage emerges during development.To elucidate the induction and molecular mechanisms which are responsible for the specification of this lineage. To make available experimental systems that will permit the screening of factors that induce a mobilization of oligodendrocyte precursors to repair demyelinating lesions.The rationale for our project stems from the observation that in Multiple Sclerosis, although in recent plaques there are attempts at remyelination, this endogenous repair process is insufficient, during the course of the disease. Therefore, it is important to increase the number of remyelinating oligodendrocytes in the vicinity of lesions by inducing or increasing the number of oligodendrocyte progenitors to migrate out from the zone where they are produced towards the plaques. These cells can then differentiate into myelinating oligodendrocytes. To reach this goal, major gaps in our present knowledge concerning the origin of oligodendrocytes await clarification. We also need to reveal the molecular events that drive stem cells or multipotential cells of the neuroepithelium in the neural tube to differentiate into oligodendrocytes. Assuming that during neural regeneration there is a recapitulation of the molecular and cellular events that take place during development, we have chosen to study the emergence of the oligodendrocyte lineage during embryonic development.To solve this question we felt absolutely vital to gather a panel of scientists i) having a common interest in the field of glial cells ii) covering a large scope of complementary domains of technical expertise, including experimental embryologists, cellular and molecular biologists, and iii) able to tackle the problem on different animal models: Drosophila, chicken and mouse. 1) The regional potentialities of the CNS to generate oligodendrocytes will be analysed using homotypic and isochronic transplantations of quail embryo neural tube portions sampled along the rostro-caudal and ventro-dorsal axis, into chick embryos. 2) The putative commitment of these neural tube territories towards the oligodendroglial lineages will be analysed both in vitro and in vivo (heterotopic and heterochronic transplantations). 3) The induction of the oligodendroglial lineage will be studied both in vitro and in vivo by examining the effects of the notochord, the foor plate and a series of candidate factors. 4) Mouse transcription factors and specific proteins that mark the commitment of neuroepithelial cells towards the oligodendrocyte lineage will be identifyed, and genes specifying the glial cell lineage, in Drosophila, isolated. 5) Transgenic mice bearing a tag to purify oligodendrocyte precursors will be generated. Fields of science natural sciencesbiological sciencesdevelopmental biologymedical and health sciencesbasic medicineneurologymultiple sclerosismedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicinetransplantationmedical and health sciencesclinical medicineembryology Programme(s) FP4-BIOMED 2 - Specific research, technological development and demonstration programme in the field of biomedicine and health, 1994-1998 Topic(s) 3.2 - Nervous system damage and repair Call for proposal Data not available Funding Scheme CSC - Cost-sharing contracts Coordinator Institut National de la Santé et de la Recherche Médicale EU contribution No data Address 47,Boulevard de l'Hôpital 75651 Paris France See on map Total cost No data Participants (6) Sort alphabetically Sort by EU Contribution Expand all Collapse all Centre National de la Recherche Scientifique France EU contribution No data Address Av.de la Belle Gabrielle 94736 Nogent-sur-Marne See on map Total cost No data Centre National de la Recherche Scientifique France EU contribution No data Address 118,Route de Narbonne 31062 Toulouse See on map Total cost No data RUPRECHT-KARLS-UNIVERSITAET HEIDELBERG Germany EU contribution No data Address Im Neuenheimer Feld 282 69120 HEIDELBERG See on map Total cost No data Universidad de Murcia Spain EU contribution No data Address Campus de Espinardo 30100 Murcia See on map Total cost No data University of Edinburgh United Kingdom EU contribution No data Address Old College South Bridge EH8 9YL Edinburgh See on map Total cost No data WESTFAELISCHE WILHELMS - UNIVERSITAET MUENSTER Germany EU contribution No data Address Badestr. 9 48149 Münster See on map Total cost No data