Fonction et Développement des Oligodendrocytes B. Zalc CRICM, UPMC-Paris 6; Inserm U975; CNRS 7225...

Fonction et Développement des Fonction et Développement des OligodendrocytesOligodendrocytes

B. ZalcCRICM, UPMC-Paris 6; Inserm U975; CNRS 7225

Hôpital de la Salpêtrièrebernard.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

- - - - - - - - - - - - - - - -

- - - - - - - - - - - - - - - -

+ + +

+ + +

+ + +

+ + +

+ + +

+ + +

+ + +

+ + +

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

- - - - - - - - - - - - - - - - - - - - -

- - - - - - - - - - - - - - - - - - - - -

+ + +

+ + ++ + + + + + +

+ + + + + + +

+ + + + + + +

+ + + + + + +

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