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Fonction et Développement des Oligodendrocytes

Fonction et Développement des Oligodendrocytes. B. Zalc CRICM, UPMC-Paris 6; Inserm U975; CNRS 7225 Hôpital de la Salpêtrière bernard.zalc@upmc.fr. 1. Généralités sur la myéline 2. Fonctions de la gaine de myéline 3. Origine des Oligodendrocytes 4. Migration des Oligodendrocytes

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Fonction et Développement des Oligodendrocytes

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  1. Fonction et Développement des Oligodendrocytes B. Zalc CRICM, UPMC-Paris 6; Inserm U975; CNRS 7225 Hôpital de la Salpêtrière bernard.zalc@upmc.fr

  2. 1. Généralités sur la myéline 2. Fonctions de la gaine de myéline 3. Origine des Oligodendrocytes 4. Migration des Oligodendrocytes 5. Développement des Oligodendrocytes

  3. 1) Généralités sur la myéline

  4. Composition biochimique de la myéline

  5. (Zalc& Lubetzki, in Multiple Sclerosis, C. Raine ed, 2008)

  6. 2) Fonctions de la gaine de myéline

  7. cm rm ri Na+ - - - - - - - - - - - - - - - - + + + + + + + + + + + + + + + + + + + + + + + + - - - - - - - - - - - - - - - - Current can go forward axially Or radially into the membrane Increase radius  

  8. 1 Unmyelinated

  9. From Peles and Salzer, 2000

  10. - - - - - - - - - - - - - - - - - - - - - + + + + + + - - - - - - - - - - - - - - - - - - - - - : Na channels Saltatory conduction + + + + + + + + + + + + + + + + + + + + + + + + + + + + Impulse jumps from node to node Latin: saltare = to jump

  11. Myelinated Unmyelinated Myelination favoured if diameter > 1 micron

  12. Contactin Nfasc155 Nfasc186 4.1B IIII- Spectrin AnkyrinB Molecular organization of CNS nodes of Ranvier and paranodes Glial Cell Node NrCAM Paranode Nav Caspr Contactin Axon IV spectrin AnkyrinG From Brophy, 2010

  13. 3) Origine des oligodendrocytes

  14. (Zalc& Colman, Science, 2000)

  15. pD pD Pax6 Irx3 Irx3 Pax6 Oligodendrocytes PDGFRa + Motor Neurons p0 p0 p1 p1 p2 p2 Nkx2.2 Olig1/2 Olig1/2 pMN pMN p3 p3 Nkx2.2 V3 Dorsalizing factors (BMPs, Wnt, dorsalin…) After E11.5 E8.5-E11.5 Ngn2 Nkx2.2 Ngn3 Ventralizing factor (Sonic hedgehog, …?) Lu et al.,2000, Zhou et al., 2001, Zhou et al. 2002, Fu et al., 2002

  16. late oligodendrocytes ~10-20% of the total early oligodendrocytes ~70-80% of the total The origin of oligodendrocytes in the rodent spinal cord early oligodendrocytes ~10-20% of the total N. Tekki-Kessaris

  17. Tekki-Kessaris & Richardson, 2006

  18. 4) Migration des oligodendrocytes

  19. Olivier et al., Development, 2001 Heterotopic grafts

  20. Spassky et al., J. Neurosci. 2002 Sema 3A Sema 3F Netrin-1 • Expression of receptors by OPCs class 3 Sema Neuropilin-1 and Neuropilin-2 /Sema 3A /Sema 3F DCC and Unc5h1 Netrin-1 (Embryonic) (Post natal) • Expression of factors in the context of the optic nerve

  21. 5) Développement des oligodendrocytes

  22. A2B5 GD3 NG2 Oligodendrocyte Precursor cell Adult Précursor Oligodendrocyte Progenitor

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