Schmucker Group

The nervous system, like the immune system, needs to generate extraordinary diversity and specificity in molecular recognition. It has been estimated that some 1012 neurons are interconnected by up to 1015 synapses in the human brain. Surprisingly, the human genome contains fewer than 30,000 genes. How is the relative small amount of genetic information utilized to specify such a complex wiring diagram ? Finding answers to this challenging question is one of our central goals. We focus our research on dissecting the developmental mechanisms that control the formation of specific neuronal circuits, with a strong focus on mechanosensory systems. We are using genetic, cell biological and biochemical methods to better understand how the molecular recognition of synaptic targets is achieved and what controls the specificity of selective synapse formation.

To tackle the complexity we aim to achieve single cell/synapse resolution in our functional in vivo analysis. In molecular terms we are focusing on the recognition specificity and signal transduction of membrane receptors, compartmentalized signaling in developmental synapse formation, morphogenetic control in shaping complex neuronal shapes. Our interest covers the areas of neural development, genetics, physiology, cell signaling, protein biochemistry, gene regulation and molecular evolution. Genetic networks of neuronal wirings ae tested in vivo in various experimental paradigms of Drosophila melanogaster and Xenopus tropicalis.

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Methods

  • Genetic screening in Drosophila melanogaster for novel regulators of neuronal wiring.
  • In vivo imaging of axon development and synaptogenesis on single cell level in Drosophila.
  • scRNAseq based transcriptome analysis in Drosophila and Xenopus tropicalis.
  • Genetic engineering of loss and gain-of function models in Xenopus.
  • In vivo imaging of axon development and synaptogenesis on single cell level in Xenopus.
  • High resolution confocal microscopy and correlative light-electron microscopy.
  • Protein biochemical analysis of transmembrane receptors and transcription factors in vivo and in cell culture models.

5 selected publications

  1. Izadifar A, Courchet J, Virga DM, Verreet T, Hamilton S, Ayaz D, Misbaer A, Vandenbogaerde S, Monteiro L, Petrovic M, Sachse S, Yan B, Erfurth ML, Dascenco D, Kise Y, Yan J, Edwards-Faret G, Lewis T, Polleux F, Schmucker D. Axon morphogenesis and maintenance require an evolutionary conserved safeguard function of Wnk kinases antagonizing Sarm and Axed. Neuron. 2021; 109(18). https://doi.org/10.15252/embj.201899669.
  2. Urwyler O, Izadifar A, Vandenbogaerde S, Sachse S, Misbaer A, Schmucker D. (2019) Branch-restricted localization of phosphatase Prl-1 specifies axonal synaptogenesis domains. Science 364(6439):eaau9952.
  3. Sachse SM, Lievens S, Ribeiro LF, Dascenco D, Masschaele D, Horré K, Misbaer A, Vanderroost N, De Smet AS, Salta E, Erfurth ML, Kise Y, Nebel S, Van Delm W, Plaisance S, Tavernier J, De Strooper B, De Wit J, Schmucker D. (2019) Nuclear import of the DSCAM-cytoplasmic domain drives signaling capable of inhibiting synapse formation. EMBO J. 38(6). pii: e99669.
  4. Dascenco D, Erfurth M-L, Izadifar A, Song M, Sachse S, Bortnick R, Urwyler O, Petrovic M, Ayaz D, He H, Kise Y, Thomas F, Kidd T, Schmucker D. (2015) Slit and Receptor Tyrosine Phosphatase 69D Confer Spatial Specificity to Axon Branching via Dscam1. Cell 162: 1140-54.
  5. He H, Kise Y, Izadifar A, Urwyler O, Ayaz D, Parthasarthy A, Yan B, Erfurth M-L, Dascenco D, and Schmucker D. (2014) Cell-intrinsic requirement of Dscam isoform diversity. Science 344: 1182-1186.