title: The L1-type cell adhesion molecule Neuroglian is necessary for maintenance of sensory axon advance in the Drosophila embryo.
abstract: BACKGROUND
  Cell adhesion molecules have long been implicated in the regulation of axon growth, but the precise cellular roles played by individual cell adhesion molecules and the molecular basis for their action are still not well understood. We have used the sensory system of the Drosophila embryo to shed light on the mechanism by which the L1-type cell adhesion molecule Neuroglian regulates axon growth.
  
  
  RESULTS
  We have found a highly penetrant sensory axon stalling phenotype in neuroglian mutant embryos. Axons stalled at a variety of positions along their normal trajectory, but most commonly in the periphery some distance along the peripheral nerve. All lateral and dorsal cluster sensory neurons examined, except for the dorsal cluster neuron dbd, showed stalling. Sensory axons were never seen to project along inappropriate pathways in neuroglian mutants and stalled axons showed normal patterns of fasciculation within nerves. The growth cones of stalled axons possessed a simple morphology, similar to their appearance in wild-type embryos when advancing along nerves. Driving expression of the wild-type form of Neuroglian in sensory neurons alone rescued the neuroglian mutant phenotype of both pioneering and follower neurons. A partial rescue was achieved by expressing the Neuroglian extracellular domain. Over/mis-expression of Neuroglian in all neurons, oenocytes or trachea had no apparent effect on sensory axon growth.
  
  
  CONCLUSIONS
  We conclude that Neuroglian is necessary to maintain axon advance along axonal substrates, but is not required for initiation of axon outgrowth, axon fasciculation or recognition of correct growth substrates. Expression of Neuroglian in sensory neurons alone is sufficient to promote axon advance and the intracellular region of the molecule is largely dispensable for this function. It is unlikely, therefore, that Nrg acts as a molecular 'clutch' to couple adhesion of F-actin within the growth cone to the extracellular substrate. Rather, we suggest that Neuroglian mediates sensory axon advance by promoting adhesion of the surface of the growth cone to its substrate. Our finding that stalling of a pioneer sensory neuron is rescued by driving Neuroglian in sensory neurons alone may suggest that Neuroglian can act in a heterophilic fashion.
authors.affiliation: Department of Anatomy and Cell Biology, University of Melbourne, VIC 3010, Australia. v.martin@unimelb.edu.au
authors.forename: Veronica
authors.initials: V
authors.lastname: Martin
authors.forename: Eli
authors.initials: E
authors.lastname: Mrkusich
authors.forename: Martin C
authors.initials: MC
authors.lastname: Steinel
authors.forename: Jason
authors.initials: J
authors.lastname: Rice
authors.forename: David J
authors.initials: DJ
authors.lastname: Merritt
authors.forename: Paul M
authors.initials: PM
authors.lastname: Whitington
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002232:Carbocyanines; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D005456:Fluorescent Dyes; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D010641:Phenotype; D011984:Sensory Receptor Cells / Q000502:physiology* / Q000648:ultrastructure
chemical_list: C035005:3,3'-dihexadecylindocarbocyanine; D002232:Carbocyanines; D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; D005456:Fluorescent Dyes; C061745:Nrg protein, Drosophila