A screen of cell-surface molecules identifies leucine-rich repeat proteins as key mediators of synaptic target selection

Neuron. 2008 Sep 25;59(6):972-85. doi: 10.1016/j.neuron.2008.07.037.


In Drosophila embryos and larvae, a small number of identified motor neurons innervate body wall muscles in a highly stereotyped pattern. Although genetic screens have identified many proteins that are required for axon guidance and synaptogenesis in this system, little is known about the mechanisms by which muscle fibers are defined as targets for specific motor axons. To identify potential target labels, we screened 410 genes encoding cell-surface and secreted proteins, searching for those whose overexpression on all muscle fibers causes motor axons to make targeting errors. Thirty such genes were identified, and a number of these were members of a large gene family encoding proteins whose extracellular domains contain leucine-rich repeat (LRR) sequences, which are protein interaction modules. By manipulating gene expression in muscle 12, we showed that four LRR proteins participate in the selection of this muscle as the appropriate synaptic target for the RP5 motor neuron.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Cell Movement / physiology
  • Databases, Protein
  • Drosophila / growth & development
  • Drosophila / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Gene Expression Profiling
  • Growth Cones / metabolism*
  • Insulin-Like Growth Factor Binding Proteins / metabolism
  • Larva / metabolism
  • Leucine
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Models, Neurological
  • Motor Neurons / cytology
  • Motor Neurons / metabolism*
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / metabolism
  • Muscles / innervation*
  • Muscles / metabolism
  • Neuromuscular Junction / growth & development*
  • Neuromuscular Junction / metabolism
  • Protein Structure, Tertiary / physiology
  • RNA, Messenger / analysis
  • Repetitive Sequences, Amino Acid


  • Drosophila Proteins
  • Insulin-Like Growth Factor Binding Proteins
  • Membrane Proteins
  • RNA, Messenger
  • acid-labile subunit, Drosophila
  • caps protein, Drosophila
  • trn protein, Drosophila
  • Leucine