CRICM, UPMC-Paris 6; Inserm U975; CNRS 7225 Hôpital de la Salpêtrière 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 5. Développement des Oligodendrocytes

1) Généralités sur la myéline

Composition biochimique de la myéline

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

2) Fonctions de la gaine de myéline

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

1 Unmyelinated

From Peles and Salzer, 2000

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

Myelinated Unmyelinated Myelination favoured if diameter > 1 micron

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

3) Origine des oligodendrocytes

(Zalc & Colman, Science, 2000)

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

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

Tekki-Kessaris & Richardson, 2006

4) Migration des oligodendrocytes

Olivier et al., Development, 2001 Heterotopic grafts

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

5) Développement des oligodendrocytes

Oligodendrocyte Precursor cell A2B5 GD3 NG2 Adult Précursor Oligodendrocyte Progenitor