Derailed regulates development of the Drosophila neuromuscular junction

Dev Neurobiol. 2008 Feb 1;68(2):152-65. doi: 10.1002/dneu.20562.

Abstract

Neural function is dependent upon the proper formation and development of synapses. We show here that Wnt5 regulates the growth of the Drosophila neuromuscular junction (NMJ) by signaling through the Derailed receptor. Mutations in both wnt5 and drl result in a significant reduction in the number of synaptic boutons. Cell-type specific rescue experiments show that wnt5 functions in the presynaptic motor neuron while drl likely functions in the postsynaptic muscle cell. Epistatic analyses indicate that drl acts downstream of wnt5 to promote synaptic growth. Structure-function analyses of the Drl protein indicate that normal synaptic growth requires the extracellular Wnt inhibitory factor domain and the intracellular domain, which includes an atypical kinase. Our findings reveal a novel signaling mechanism that regulates morphology of the Drosophila NMJ.

Publication types

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

MeSH terms

  • Animals
  • Body Patterning / genetics
  • Cell Differentiation / genetics
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development*
  • Drosophila melanogaster / metabolism*
  • Gene Expression Regulation, Developmental / genetics
  • Motor Neurons / cytology
  • Motor Neurons / metabolism
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism
  • Mutation / genetics
  • Neuromuscular Junction / genetics
  • Neuromuscular Junction / growth & development*
  • Neuromuscular Junction / metabolism*
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / ultrastructure
  • Protein Structure, Tertiary / genetics
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction / genetics
  • Synaptic Transmission / genetics
  • Wnt Proteins / chemistry
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*

Substances

  • Drosophila Proteins
  • Proto-Oncogene Proteins
  • Wnt Proteins
  • Wnt5 protein, Drosophila
  • DRL protein, Drosophila
  • Receptor Protein-Tyrosine Kinases