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SUMMARY:Localised RNA-based mechanisms underlie neuronal wiring - Christin
 e Holt
DTSTART:20171204T110000Z
DTEND:20171204T120000Z
UID:TALK86091@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:Our research aims to understand how neural circuits become wir
 ed-up properly in the developing brain and how they are maintained into ma
 turity. Emerging evidence points to an increasingly important role for pos
 t-translational mechanisms such as RNA localization and local protein synt
 hesis in axons. RNA localization enables nascent proteins to be positioned
  at precise subcellular locations facilitating localized growth responses 
 to extrinsic signals. Our work has shown that extrinsic signals trigger ra
 pid de novo synthesis in axonal growth cones and that local translation is
  critical for directional steering. I will present our recent in vivo work
  using the Axon-TRAP-RiboTag approach in the mouse to analyse mRNA transla
 tion in axons (Shigeoka et al\, Cell 2016). This study reveals that the yo
 ung (embryonic-to-postnatal) axonal translatome comprises an evolving subs
 et of enriched genes with axon-specific roles. Adult axons\, remarkably\, 
 have a complex translatome with strong links to axon survival\, neurotrans
 mission\, and neurodegenerative disease. I will also present live imaging 
 studies in which simultaneous tracking of RNA granule dynamics and axonal 
 morphology in vivo demonstrates that RNA granules dock at sites of branch 
 emergence and invade stabilised branches (Wong et al\, Neuron 2017). The d
 ata demonstrate a requirement for local protein synthesis in building arbo
 r complexity and suggest a key role for local translation in neuronal remo
 delling.\nShigeoka T\, Jung H\, Jung J\, Turner-Bridger\, B\, Ohk J\, Lin 
 JQ\, Amieux PS\, Holt CE. Dynamic axonal translation in developing and mat
 ure visual circuits. Cell. Jun 30\; 166(1):181-92 (2016).\nWong HH\, Lin J
 Q\, Ströhl F\, Roque CG\, Cioni\, JM\, Cagnetta R\, Turner-Bridger B\, La
 ine R\, Harris WA\, Kaminski CF\, Holt CE. RNA docking and local translati
 on regulate site-specific axon remodelling in vivo. Neuron. Aug 16 95(4):8
 52-868.e8. (2017).\n\n\n
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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