Fonction et Développement des Fonction et Développement des OligodendrocytesOligodendrocytes
B. ZalcCRICM, UPMC-Paris 6; Inserm U975; CNRS 7225
Hôpital de la Salpêtriè[email protected]
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
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Current can go forward axially
Or radially into the membrane
ri
cm rmIncrease radius
Na+
Unmyelinated
1
From Peles and Salzer, 2000
: Na channels
Saltatory conduction
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Impulse jumps fromnode to node
Latin: saltare = to jump
Unmyelinated
Myelinated
Myelination favoured if diameter > 1 micron
NrCAM
Nav
Contactin
Caspr
AnkyrinGIV spectrinAxonIIII-Spectrin AnkyrinB
4.1B
Nfasc155Nfasc186
Contactin
Molecular organization of CNS nodes of Ranvier and paranodes
Paranode
Glial Cell
Node
From Brophy, 2010
3) Origine des oligodendrocytes
(Zalc & Colman, Science, 2000)
p3
pMN
p2
p1
p0
pD
p3
pMN
p2
p1
p0
pD
Ngn2Olig1/2
Irx3
Dorsalizing factors (BMPs, Wnt, dorsalin…)
Ventralizing factor (Sonic hedgehog, …?)
Pax6
Nkx2.2
Olig1/2
Irx3
Nkx2.2
Nkx2.2
E8.5-E11.5After E11.5
Lu et al.,2000, Zhou et al., 2001, Zhou et al. 2002, Fu et al., 2002
Pax6
Ngn3
MotorNeurons
OligodendrocytesPDGFR +
V3
The origin of oligodendrocytes in the rodent spinal cord
early oligodendrocytes~70-80% of the total
late oligodendrocytes~10-20% of the total
N. Tekki-Kessaris
early oligodendrocytes~10-20% of the
total
Tekki-Kessaris & Richardson, 2006
4) Migration des oligodendrocytes
Olivier et al., Development, 2001
Heterotopic grafts
Spassky et al., J. Neurosci. 2002
• Expression of receptors by OPCs
Netrin-1(Post natal)(Embryonic)
DCC and Unc5h1
class 3 Sema Neuropilin-1 and Neuropilin-2/Sema 3A /Sema 3F
• Expression of factors in the context of the optic nerve
Sema 3ASema 3FNetrin-1
5) Développement des
oligodendrocytes
Oligodendrocyte Progenitor
Oligodendrocyte Precursor cell
Adult Précursor
A2B5GD3NG2