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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
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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 10mm 10mm horizontal branch midline Srausfeld et al., MRT 2003 10mm 10mm
The drl Receptor Tyrosine Kinase Fradkin et al., TINS 2010
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
MARCM clones -/- -/- -/- +/- mutant phenotype mutant phenotype ? cell-autonomous ?
-/- -/- 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 growth in an intrinsic manner
A growing b axon b axon WNT5 axonal growth ? Secreted protein Transmembrane receptor
A stoping b axon extrinsic MB axon b axon WNT5 stop ? LIO RTK
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
Wnt/Ryk-mediated axon repulsion counterbalances ephrinB1/EphB-mediated attraction in retinotopic mapping