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SUMMARY:Molecular Mechanisms of Axon Branching and Synoptogenicsm in Fly a
 nd Frog CNS - Dietmar Schmucker. VIB Vesalius Research Centre\, KULeuven
DTSTART:20150126T163000Z
DTEND:20150126T180000Z
UID:TALK56603@talks.cam.ac.uk
CONTACT:P.H. Marchington
DESCRIPTION:The overall goal of our research is to dissect developmental m
 echanisms that control the formation of specific neuronal circuits. We are
  using genetic\, cell biological\, biochemical and structural methods to b
 etter understand how the molecular specification of synaptic targets is ac
 hieved. In much of our work we are taking advantage of the powerful geneti
 c tools available for the model organism Drosophila. However we have recen
 tly started to also extend our studies to the analysis of neural circuit f
 ormation in vertebrates. Specifically we are using the model organism Xeno
 pus tropicalis and combine biochemical\, reverse genetic as well as imagin
 g techniques for a dissection of neural circuit formation.\n\nConcerning t
 he cellular mechanisms of neuronal wiring we are focusing on two developme
 ntal processes that are still poorly understood: Axonal branching and cent
 ral synapse formation/selection. In order to do so we developed new geneti
 c labeling methods to visualize single axons and single pre-synapses withi
 n the CNS. These techniques allow us to resolve important steps underlying
  axon branching and synapse formation. They also allow us to conduct a gen
 etic dissection of the underlying regulatory pathways (Urwyler et al. (201
 5)\, Development).\n\nFor the investigation of molecular mechanisms we hav
 e been focusing on the recognition specificity and signal transduction of 
 membrane receptors of the Immunoglobulin superfamily (Ig-SF). Specifically
 \, we have been studying the function of the Ig-domain containing neuronal
  receptor “Dscam” in flies. The Drosophila Dscam receptor is closely r
 elated to the human protein Down syndrome cell adhesion molecule (DSCAM). 
 Through alternative splicing the Drosophila Dscam gene  gives rise to thou
 sands of receptors with diverse ectodomains (18\,496) thought to provide h
 omophilic and possibly heterophilic recognition specificity for neuronal w
 iring (Schmucker et al.\, (2000)\, Cell\; Sun et al. (2013)\, EMBO J.)\n\n
 Recently we discovered that the diversity of Dscam1 isoforms is also utili
 zed cell-intrinsically where it is essential for complex axonal branching 
 of sensory neurons. Genetic and single cell analysis suggest that the qual
 itative (i.e. structural) differences between isoforms serve as a rheostat
  to achieve quantitative control of Dscam1 signaling within axonal growth 
 cones (He et al. (2014)\, Science).\n\nFor more information please see rec
 ent publications:\n\nUrwyler\, O.\, Izadifar\, A.\, Dascenco\, D.\, Petrov
 ic\, M.\, He H.\, Ayaz D.\, Kremer A.\, Lippens S.\, Baatsen\, P.\, Guéri
 n\, C.J. & Schmucker\, D. Investigating CNS synaptogenesis at single-synap
 se resolution by combining reverse genetics with correlative light and ele
 ctron microscopy. Development. 2015\;142(2):394-405.\n\nHe\, H.\, Kise\, Y
 .\, Izadifar\, A.\, Urwyler\, O.\, Ayaz D.\, Parthasarthy\, A.\, Yan\, B.\
 , Erfurth\, M.L.\, 7Dascenco\, D. & Schmucker\, D. Cell-intrinsic requirem
 ent of Dscam1 isoform diversity for axon collateral formation. Science. 20
 14\; 344(6188):1182-6.\n\nKise\, Y. & Schmucker\, D. Role of self-avoidanc
 e in neuronal wiring.\nCurr Opin Neurobiol. 2013\, 23(6):983-9.\n\nSun W\,
  You X\, Gogol-Döring A\, He H\, Kise Y\, Sohn M\, Chen T\, Klebes A\, Sc
 hmucker D\, Chen W. Ultra-deep profiling of alternatively spliced Drosophi
 la Dscam isoforms by circularization-assisted multi-segment sequencing. EM
 BO J. 2013 \;32(14):2029-38.\n
LOCATION:The Hodgkin Huxley Seminar Room\, Department of Physiology Develo
 pment and Neuroscience
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