Les power point sont sur le site du Master BS, dans l’onglet de l’UE FMBS106

www.masterbs.univ-montp2.fr

Guidage axonal - Développement du cerveau - Remodelage neuronal - Mémoire

1) Attraction by the midline

2) Crossing the midline

3) Molecular changes before and after the crossing

4) AC or PC ? (DRL/WNT5)

5) Fasciculation

Book chapter Navigating intermediate targets: the nervous system midline Dickson and Zou in Cold Spring Harbor Perspect Biol 2010(Neuronal guidance - the biology of brain wiring)

Commissural axons at the midline in vertebrates and Drosophila

Morphogens involved in neuronal guidance and their receptors

Netrins, Slits and their receptors.

Receptor for attraction (DCC)

Receptors for repulsion (UNC5 for Netrins; Robo for Slits)

Guidance-cue receptor signaling strategies.

Mutipe guidance cues control the pathfindingof spinal cord commissuralaxons along the dorso-ventral axis

Midline crossing mutants in Drosophila

Fig. 5.39 in Development ofthe nervous system (book)

Molecular cues controlling the pathway choices at the Drosophila midline:COMM regulates ROBO1 trafficking and midline crossing

Molecular cues controlling the pathway choices at the vertebrate midline:the Slit/Robo and Sema3B, 3F/Neuropilin2systems control midline guidance

A Robo code for lateral positioning

Drosophila ventral nerve cord

Rodent spinal cord

DRL/WNT5 in the Drosophila brain:Grillenzoni et al., Development 2007

Mamalian Ryks in the developing nervous system:Fradkin et al., Trends in Neurosciences 2010

Rein et al., 2002 Current Biology

The mushroom bodies (MBs) in theadult Drosophila brain

midline horizontal branch

Srausfeld et al., MRT 2003 10m

A wild-type neuron

vertical branch10m10m

10m

The drl Receptor Tyrosine Kinase

Fradkin et al., TINS 2010

DRL is not expressed in the MBs (FASII)

DRL is not expressed in the MBs (FASII)

DRL in the embryonic brain

drl LOF mutation induces no apparent defects in the embryonic brainbut do induce defects in the embryonic nerve cord

drl is not expressed in the MB neurons but is required for the MB development

Grillenzoni et al., Development 2007

-/-

+/--/-

mutant phenotype ?mutant phenotype

-/-

cell-autonomous ?

MARCM clones

-/-

-/-

mutant phenotype

-/-

+/-

No mutant phenotype, therefore non cell-autonomous

+/+

+/+

Wnt5-/Y; -GAL4 UAS-mGFP/+

Wnt5-/Y; -GAL4 UAS-mGFP/+; UAS-Wnt5/+

Conclusions:Wnt5 is necessary for the axonal growthin an intrinsic manner

axon

WNT5?

Secreted protein

Transmembranereceptor

axonalgrowth

A growing axon

axon

extrinsic MB axon

LIOstop WNT5?

RTK

A stoping axon

Structural features of Ryk subfamily receptors

Cleavage and nuclear translocation of the Ryk intracellular domain (ICD) mediates neurogenesis

Wnt/Ryk-mediated axon repulsion in thedeveloping versus injured adult spinal cord

Ephrins and their Eph receptors

Wnt/Ryk-mediated axon repulsion counterbalances ephrinB1/EphB-mediatedattraction in retinotopic mapping