Highwire regulates synaptic growth in Drosophila

Neuron. 2000 May;26(2):313-29. doi: 10.1016/s0896-6273(00)81166-6.


The formation, stabilization, and growth of synaptic connections are dynamic and highly regulated processes. The glutamatergic neuromuscular junction (NMJ) in Drosophila grows new boutons and branches throughout larval development. A primary walking behavior screen followed by a secondary anatomical screen led to the identification of the highwire (hiw) gene. In hiw mutants, the specificity of motor axon pathfinding and synapse formation appears normal. However, NMJ synapses grow exuberantly and are greatly expanded in both the number of boutons and the extent and length of branches. These synapses appear normal ultrastructurally but have reduced quantal content physiologically. hiw encodes a large protein found at presynaptic terminals. Within presynaptic terminals, HIW is localized to the periactive zone surrounding active zones; Fasciclin II (Fas II), which also controls synaptic growth, is found at the same location.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Chromosome Mapping
  • Drosophila / genetics
  • Drosophila / growth & development
  • Drosophila / physiology*
  • Drosophila Proteins*
  • Growth Cones / metabolism
  • Humans
  • Molecular Sequence Data
  • Mutation / physiology
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Neuromuscular Junction / ultrastructure
  • Peptide Fragments / genetics
  • Peptide Fragments / physiology
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / ultrastructure
  • Sequence Homology, Amino Acid
  • Synapses / physiology*
  • Synapses / ultrastructure
  • Tissue Distribution
  • Transcription, Genetic


  • Drosophila Proteins
  • HIW protein, Drosophila
  • Nerve Tissue Proteins
  • Peptide Fragments

Associated data

  • GENBANK/AF262977