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Les power point sont sur le site du Master BS, dans l’onglet de l’UE FMBS106
Guidage axonal - Développement du cerveau - Remodelage neuronal - Mémoire
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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)
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Commissural axons at the midline in vertebrates and Drosophila
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Morphogens involved in neuronal guidance and their receptors
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Netrins, Slits and their receptors.
Receptor for attraction (DCC) Receptors for repulsion (UNC5 for Netrins; Robo for Slits)
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Guidance-cue receptor signaling
strategies.
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Mutipe guidance cues control the pathfinding of spinal cord commissural axons along the dorso-ventral axis
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Midline crossing mutants in
Drosophila Fig in Development of the nervous system (book)
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Molecular cues controlling the pathway choices at the Drosophila midline:
COMM regulates ROBO1 trafficking and midline crossing
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Molecular cues controlling the pathway choices at the vertebrate midline:
the Slit/Robo and Sema3B, 3F/Neuropilin2 systems control midline guidance
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Drosophila ventral nerve cord
A Robo code for lateral positioning Rodent spinal cord
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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
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The mushroom bodies (MBs) in the adult Drosophila brain
Rein et al., 2002 Current Biology
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A wild-type neuron vertical branch horizontal branch midline
10mm 10mm vertical branch horizontal branch midline Srausfeld et al., MRT 2003 10mm 10mm
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The drl Receptor Tyrosine Kinase
Fradkin et al., TINS 2010
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DRL is not expressed in the MBs (FASII)
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DRL is not expressed in the MBs (FASII)
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DRL in the embryonic brain
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drl LOF mutation induces no apparent defects in the embryonic brain
but do induce defects in the embryonic nerve cord
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drl is not expressed in the MB neurons but is
required for the MB development Grillenzoni et al., Development 2007
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-/- -/- -/- +/- mutant phenotype mutant phenotype ? cell-autonomous ?
MARCM clones -/- -/- -/- +/- mutant phenotype mutant phenotype ? cell-autonomous ?
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-/- -/- mutant phenotype
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+/+ -/- +/+ +/- No mutant phenotype, therefore non cell-autonomous
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Wnt5-/Y; -GAL4 UAS-mGFP/+
UAS-Wnt5/+ Conclusions: Wnt5 is necessary for the axonal growth in an intrinsic manner
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A growing b axon Secreted Transmembrane receptor protein b axon axonal
WNT5 axonal growth ? Transmembrane receptor Secreted protein
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A stoping b axon extrinsic MB axon b axon WNT5 stop ? LIO RTK
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Structural features of Ryk subfamily receptors
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Cleavage and nuclear translocation of the Ryk intracellular domain (ICD)
mediates neurogenesis
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Wnt/Ryk-mediated axon repulsion in the
developing versus injured adult spinal cord
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Ephrins and their Eph receptors
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Wnt/Ryk-mediated axon repulsion counterbalances ephrinB1/EphB-mediated
attraction in retinotopic mapping
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