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.

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Presentation transcript:

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 pathfinding of spinal cord commissural axons along the dorso-ventral axis

Midline crossing mutants in Drosophila Fig. 5.39 in Development of the 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/Neuropilin2 systems control midline guidance

Drosophila ventral nerve cord A Robo code for lateral positioning 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

The mushroom bodies (MBs) in the adult Drosophila brain Rein et al., 2002 Current Biology

A wild-type  neuron  vertical branch  horizontal branch midline 10mm 10mm  vertical branch  horizontal branch midline Srausfeld et al., MRT 2003 10mm 10mm

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 brain but 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 mutant phenotype ? cell-autonomous ?

-/- -/- mutant phenotype

+/+ -/- +/+ +/- No mutant phenotype, therefore non cell-autonomous

Wnt5-/Y; -GAL4 UAS-mGFP/+ UAS-Wnt5/+ Conclusions: Wnt5 is necessary for the axonal growth in an intrinsic manner

A growing b axon Secreted Transmembrane receptor protein b axon axonal WNT5 axonal growth ? Transmembrane receptor Secreted protein

A stoping b axon extrinsic MB axon b axon WNT5 stop ? LIO RTK

Structural features of Ryk subfamily receptors

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

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

Ephrins and their Eph receptors

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