Genetics and neurobiology of C. elegans

Principal investigator: Jean-Louis BESSEREAU

C. elegans | synapse | neuromuscular junction | GABA receptors | Acetylcholine receptors | aging | genetics | molecular neurobiology | electrophysiology | optogenetics | super-resolution microscopy | electron microscopy

 Synapses are sophisticated nanomachines that support transfer and processing of information between excitable cells.

Since most neurons receive thousands of synaptic inputs, the neuronal membrane is a mosaic of specialized microdomains where neurotransmitter receptors cluster in register with the corresponding presynaptic neurotransmitter release sites. Our lab is interested in identifying the cellular and molecular mechanisms involved in the organization and maintenance of the synapse with a specific focus on the control of neurotransmitter receptor expression and localization.
Our strategy is based on the combination of genetics, imaging, electrophysiology and biochemistry in the nematode Caenorhabditis elegans (for more information on C. elegans see “an overview of the model organism C. elegans“). Using the neuromuscular synapse as a model synapse, we identified several new genes involved in the clustering of acetylcholine and GABAA receptors through previously undescribed mechanisms, including a novel anterograde synaptic organizer that assembles extracellular scaffolds in the synaptic cleft. We are currently analyzing the organization, dynamics and maintenance of these synaptic scaffolds as well as the genes involved in the biosynthesis and trafficking of the receptors.
Our results should contribute to a better understanding of the normal and pathological synapse. Specifically, synaptic defects have been involved over the last years in the pathogenesis of a growing number of neuropsychiatric diseases, leading to the concept of “synaptopathies”. However, a number of genes linked to neuropsychiatric diseases have no assigned function, and it is likely that the mutational landscape of these diseases will be complexified by the wealth of data generated with next generation sequencing techniques. Simple organisms should help!

Join the team

We have currently no funded position but we are always looking for talented and highly motivated students or postdocs.

Team members

  • Jean-Louis BESSEREAUProfessor, UCBL
  • Allan ALCOLEIPhD Student
  • Mélissa CIZERONPost-doc
  • Manuela D’ALESSANDROResearcher, INSERM
  • Franklin FLORINPhD Student
  • Evan GOUYResearcher, HCL
  • Laure GRANGERResearch Assistant, CNRS
  • Maëlle JOSPINAssistant Professor, UCBL, HDR
  • Driss LAABIDResearch Assistant, UCBL
  • Morgane MIALONPhD Student
  • Laurent MOLINResearch Assistant, CNRS
  • Minh Dao NGUYENPhD Student
  • Bérangère PINAN-LUCARRÉ — CVResearcher, INSERM, HDR
  • Charline ROYPhD Student
  • Florence SOLARIResearcher, INSERM

Selected publications

  1. Specific heparan sulfate modifications stabilize the synaptic organizer MADD-4/Punctin at Caenorhabditis elegans neuromuscular junctions.
    Cizeron M, Granger L, Bülow HE, Bessereau JL.
    Genetics (2021) — Show abstract
  2. The HSPG Syndecan is a core organizer of cholinergic synapses.
    Zhou X, Vachon C, Cizeron M, Romatif O, Bülow HE, Jospin M, Bessereau JL.
    J Cell Biol (2021) — Show abstract
  3. The netrin receptor UNC-40/DCC assembles a postsynaptic scaffold and sets the synaptic content of GABAA receptors.
    Zhou X, Gueydan M, Jospin M, Ji T, Valfort A, Pinan-Lucarré B, Bessereau JL.
    Nature Communication (2020) — Show abstract
  4. CRELD1 is an evolutionarily-conserved maturational enhancer of ionotropic acetylcholine receptors.
    D’Alessandro M, Richard M, Stigloher C, Gache V, Boulin T, Richmond JE, Bessereau JL.
    Elife (2018) — Show abstract
  5. UNC-120/SRF independently controls muscle aging and lifespan in Caenorhabditis elegans.
    Mergoud Dit Lamarche A, Molin L, Pierson L, Mariol MC, Bessereau JL, Gieseler K, Solari F.
    Aging Cell (2018) — Show abstract
  6. Preventing Illegitimate Extrasynaptic Acetylcholine Receptor Clustering Requires the RSU-1 Protein.
    Pierron M, Pinan-Lucarré B, Bessereau JL.
    Journal of Neuroscience (2016) — Show abstract
  7. C. elegans Punctin Clusters GABA(A) Receptors via Neuroligin Binding and UNC-40/DCC Recruitment.
    Tu H, Pinan-Lucarré B, Ji T, Jospin M, Bessereau JL.
    Neuron (2016) — Show abstract
  8. Transcriptional coordination of synaptogenesis and neurotransmitter signaling.
    Kratsios P, Pinan-Lucarré B, Kerk SY, Weinreb A, Bessereau JL, Hobert O.
    Current Biology (2015) — Show abstract
  9. C. elegans Punctin specifies cholinergic versus GABAergic identity of postsynaptic domains.
    Pinan-Lucarré B, Tu H, Pierron M, Cruceyra PI, Zhan H, Stigloher C, Richmond JE, Bessereau JL.
    Nature (2014) — Show abstract
  10. Biosynthesis of ionotropic acetylcholine receptors requires the evolutionarily conserved ER membrane complex.
    Richard M, Boulin T, Robert VJ, Richmond JE, Bessereau JL.
    PNAS (2013) — Show abstract
  11. Positive modulation of a Cys-loop acetylcholine receptor by an auxiliary transmembrane subunit.
    Boulin T, Rapti G, Briseño-Roa L, Stigloher C, Richmond JE, Paoletti P, Bessereau JL.
    Nature Neuroscience (2012) — Show abstract
  12. A secreted complement-control-related protein ensures acetylcholine receptor clustering.
    Gendrel M, Rapti G, Richmond JE, Bessereau JL.
    Nature (2009) — Show abstract
  13. Eight genes are required for functional reconstitution of the Caenorhabditis elegans levamisole-sensitive acetylcholine receptor.
    Boulin T, Gielen M, Richmond JE, Williams DC, Paoletti P, Bessereau JL.
    PNAS (2008) — Show abstract
  14. A transmembrane protein required for acetylcholine receptor clustering in Caenorhabditis elegans.
    Gally C, Eimer S, Richmond JE, Bessereau JL.
    Nature (2004) — Show abstract

Funding & Support

  • Agence Nationale de la Recherche
  • Labex CORTEX website
  • 2016-2021 AFM TéléthonAlliance MyoNeurALP
  • 2015-2021 European Research Council
AFM TéléthonAgence Nationale de la Recherche
European Research Council