Development and pathologies of neuromuscular junctions

img_20140526_122700-retouchee2Extra­cel­lu­lar matrix pro­teins and adhe­sion pro­teins involved in synapse for­ma­tion, its plas­tic­i­ty and the estab­lish­ment of neu­ronal conec­tiv­i­ty. They also coor­di­nate the pre- and post­sy­nap­tic activ­i­ties and the mat­u­ra­tion of the synapse in the ner­vous sys­tem. To date, how­ev­er their are few datas that high­light mol­e­c­u­lar mecan­isms to which that matri­cials mol­e­cules con­trol the synap­tic devel­op­ment. How Extra­cel­lu­lar matrix pro­teins con­trol the main steps of the synapse’s for­ma­tion like the axon­al guid­ance, the for­ma­tion and mat­u­ra­tion of the synap­tic con­tact ? In order to answer this ques­tions, the bio­log­i­cal sys­tem used by our team is the neu­ro­mus­cu­lar junc­tion in ver­te­brates. This synapse is an excel­lent mod­èle for the study of synap­to­ge­n­e­sis and has allowed notable steps for­ward in this domain.

The main goal of our team is :

  1. Iden­ti­fy pro­teins involved in axon­al guid­ance toward their tar­get­ed muscules
  2. Reveal inter­ac­tions of a spe­cif­ic col­la­gen, CoIQ with oth­ers Extra­cel­lu­lar Matrix pro­teins and to dis­sect the sigal­i­sa­tion cas­cade induced byCoIQ in the post­sy­nap­tic element’s formation.
  3. Under­stand micro­tubules and asso­ci­at­ed pro­teins (MAP) role in the trans­duc­tion of a sig­nal com­ing from the extra­cel­lu­lar matrix.

To answer to these ques­tions, we com­bine In vivo stud­ies in knock-out mice and in vit­ro in cul­ture sys­tems. These 3 themes are asso­ci­at­ed to synapse’s patholo­gies which are stud­ied in par­al­lel on ani­mal mod­els  for these pathologies

Themes of research :

  • Iden­ti­fi­ca­tion of mol­e­cules of axon­al guid­ance involved in the for­ma­tion of the neu­ro­mus­cu­lar junction.
    Lau­re Strochlic
  • Iden­ti­fi­ca­tion of the CoIQ’s part­ners in the extra­cel­lu­lar matrix and dis­sec­tion of the sig­nal­ing cas­cade induced by the pro­tein CoIQ in the mat­u­ra­tion of the post­sy­nap­tic element.
    Alexan­dre Dobbertin

Collaborations :

  • Uni­ver­si­ty of Ottawa, Canada
  • UMR 5161 CNRS-ENSLy­on-INRA, France
  • UMR 5534 CNRS-Uni­ver­sité Lyon 1, France

Team leader