Analysis of Dscam diversity in regulating axon guidance in Drosophila mushroom bodies

Neuron. 2004 Sep 2;43(5):673-86. doi: 10.1016/j.neuron.2004.07.020.


Dscam is an immunoglobulin (Ig) superfamily member that regulates axon guidance and targeting in Drosophila. Alternative splicing potentially generates 38,016 isoforms differing in their extracellular Ig and transmembrane domains. We demonstrate that Dscam mediates the sorting of axons in the developing mushroom body (MB). This correlates with the precise spatiotemporal pattern of Dscam protein expression. We demonstrate that MB neurons express different arrays of Dscam isoforms and that single MB neurons express multiple isoforms. Two different Dscam isoforms differing in their extracellular domains introduced as transgenes into single mutant cells partially rescued the mutant phenotype. Expression of one isoform of Dscam in a cohort of MB neurons induced dominant phenotypes, while expression of a single isoform in a single cell did not. We propose that different extracellular domains of Dscam share a common function and that differences in isoforms expressed on the surface of neighboring axons influence interactions between them.

Publication types

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

MeSH terms

  • Alternative Splicing / genetics
  • Amino Acid Sequence / genetics
  • Animals
  • Animals, Genetically Modified
  • Base Sequence / genetics
  • Brain / cytology
  • Brain / embryology*
  • Brain / metabolism
  • Cell Adhesion Molecules
  • Cell Communication / genetics
  • Cell Differentiation / genetics*
  • Drosophila Proteins*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / metabolism
  • Exons / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Molecular Sequence Data
  • Mushroom Bodies / cytology
  • Mushroom Bodies / embryology*
  • Mushroom Bodies / metabolism
  • Mutation / genetics
  • Phenotype
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary / genetics
  • Proteins / genetics
  • Proteins / metabolism*
  • Transgenes / genetics


  • Cell Adhesion Molecules
  • Drosophila Proteins
  • Dscam1 protein, Drosophila
  • Protein Isoforms
  • Proteins