Regulation of Drosophila Brain Wiring by Neuropil Interactions via a Slit-Robo-RPTP Signaling Complex

Dev Cell. 2016 Oct 24;39(2):267-278. doi: 10.1016/j.devcel.2016.09.028.


The axonal wiring molecule Slit and its Round-About (Robo) receptors are conserved regulators of nerve cord patterning. Robo receptors also contribute to wiring brain circuits. Whether molecular mechanisms regulating these signals are modified to fit more complex brain wiring processes is unclear. We investigated the role of Slit and Robo receptors in wiring Drosophila higher-order brain circuits and identified differences in the cellular and molecular mechanisms of Robo/Slit function. First, we find that signaling by Robo receptors in the brain is regulated by the Receptor Protein Tyrosine Phosphatase RPTP69d. RPTP69d increases membrane availability of Robo3 without affecting its phosphorylation state. Second, we detect no midline localization of Slit during brain development. Instead, Slit is enriched in the mushroom body, a neuronal structure covering large areas of the brain. Thus, a divergent molecular mechanism regulates neuronal circuit wiring in the Drosophila brain, partly in response to signals from the mushroom body.

Keywords: Drosophila; axon growth; axon guidance; brain wiring; mushroom body; neural circuit development; receptor protein tyrosine phosphatase; robo; slit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Brain / metabolism*
  • Cell Membrane / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Epistasis, Genetic
  • Gene Expression Regulation, Developmental
  • HEK293 Cells
  • Humans
  • Larva / metabolism
  • Multiprotein Complexes / metabolism
  • Mushroom Bodies / metabolism
  • Nerve Net / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuropil / metabolism*
  • Phenotype
  • Receptor-Like Protein Tyrosine Phosphatases / metabolism*
  • Receptors, Immunologic / metabolism*
  • Signal Transduction*


  • Drosophila Proteins
  • Multiprotein Complexes
  • Nerve Tissue Proteins
  • Receptors, Immunologic
  • robo3 protein, Drosophila
  • sli protein, Drosophila
  • PTP69D protein, Drosophila
  • Receptor-Like Protein Tyrosine Phosphatases