title: Rostral growth of commissural axons requires the cell adhesion molecule MDGA2.
abstract: BACKGROUND
  Long-distance axonal growth relies on the precise interplay of guidance cues and cell adhesion molecules. While guidance cues provide positional and directional information for the advancing growth cone, cell adhesion molecules are essential in enabling axonal advancement. Such a dependence on adhesion as well as guidance molecules can be well observed in dorsal commissural interneurons, which follow a highly stereotypical growth and guidance pattern. The mechanisms and molecules involved in the attraction and outgrowth towards the ventral midline, the axon crossing towards the contralateral side, the rostral turning after midline crossing as well as the guidance along the longitudinal axis have been intensely studied. However, little is known about molecules that provide the basis for commissural axon growth along the anterior-posterior axis.
  
  
  RESULTS
  MDGA2, a recently discovered cell adhesion molecule of the IgCAM superfamily, is highly expressed in dorsolaterally located (dI1) spinal interneurons. Functional studies inactivating MDGA2 by RNA interference (RNAi) or function-blocking antibodies demonstrate that either treatment results in a lack of commissural axon growth along the longitudinal axis. Moreover, results from RNAi experiments targeting the contralateral side together with binding studies suggest that homophilic MDGA2 interactions between ipsilaterally projecting axons and post-crossing commissural axons may be the basis of axonal growth along the longitudinal axis.
  
  
  CONCLUSIONS
  Directed axonal growth of dorsal commissural interneurons requires an elaborate mixture of instructive (guidance) and permissive (outgrowth supporting) molecules. While Wnt and Sonic hedgehog (Shh) signalling pathways have been shown to specify the growth direction of post-crossing commissural axons, our study now provides evidence that homophilic MDGA2 interactions are essential for axonal extension along the longitudinal axis. Interestingly, so far each part of the complex axonal trajectory of commissural axons uses its own set of guidance and growth-promoting molecules, possibly explaining why such a high number of molecules influencing the growth pattern of commissural interneurons has been identified.
authors.affiliation: Brain Research Institute, University of Zurich and Swiss Federal Institute of Technology (ETH), Department of Biology, 8057 Zurich, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Joset
authors.forename: Andrin
authors.initials: A
authors.lastname: Wacker
authors.forename: Régis
authors.initials: R
authors.lastname: Babey
authors.forename: Esther A
authors.initials: EA
authors.lastname: Ingold
authors.forename: Irwin
authors.initials: I
authors.lastname: Andermatt
authors.forename: Esther T
authors.initials: ET
authors.lastname: Stoeckli
authors.forename: Matthias
authors.initials: M
authors.lastname: Gesemann
mesh_terms: D000596:Amino Acids; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002461:Cell Line, Transformed; D002642:Chick Embryo; D007839:Functional Laterality; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005727:Ganglia, Spinal; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020439:Growth Cones / Q000378:metabolism; D006801:Humans; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D011984:Sensory Receptor Cells / Q000166:cytology* / Q000187:drug effects; D013116:Spinal Cord / Q000166:cytology; D014162:Transfection / Q000379:methods
chemical_list: D000596:Amino Acids; D000906:Antibodies; D058851:GPI-Linked Proteins; C544522:MDGA2 protein, human; D019006:Neural Cell Adhesion Molecules; D034741:RNA, Small Interfering; C098463:dolaisoleucine