Interactions between the Ig-Superfamily Proteins DIP-α and Dpr6/10 Regulate Assembly of Neural Circuits

Neuron. 2018 Dec 19;100(6):1369-1384.e6. doi: 10.1016/j.neuron.2018.11.001. Epub 2018 Nov 19.


Drosophila Dpr (21 paralogs) and DIP proteins (11 paralogs) are cell recognition molecules of the immunoglobulin superfamily (IgSF) that form a complex protein interaction network. DIP and Dpr proteins are expressed in a synaptic layer-specific fashion in the visual system. How interactions between these proteins regulate layer-specific synaptic circuitry is not known. Here we establish that DIP-α and its interacting partners Dpr6 and Dpr10 regulate multiple processes, including arborization within layers, synapse number, layer specificity, and cell survival. We demonstrate that heterophilic binding between Dpr6/10 and DIP-α and homophilic binding between DIP-α proteins promote interactions between processes in vivo. Knockin mutants disrupting the DIP/Dpr binding interface reveal a role for these proteins during normal development, while ectopic expression studies support an instructive role for interactions between DIPs and Dprs in circuit development. These studies support an important role for the DIP/Dpr protein interaction network in regulating cell-type-specific connectivity patterns.

Keywords: DIP/Dpr proteins; cell survival; connectome; development; layer-specific circuit; specificity; synapse.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Clustered Regularly Interspaced Short Palindromic Repeats / physiology
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Gene Expression Regulation, Developmental / genetics*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Medulla Oblongata / cytology
  • Medulla Oblongata / growth & development
  • Mutation / genetics
  • Neuropil / metabolism*
  • Protein Interaction Maps
  • Surface Plasmon Resonance
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection
  • Visual Pathways / metabolism


  • DISCO Interacting Protein 1, Drosophila
  • Drosophila Proteins
  • GAL4 protein, Drosophila
  • Transcription Factors
  • Green Fluorescent Proteins