DISCO Interacting Protein 2 regulates axonal bifurcation and guidance of Drosophila mushroom body neurons

Dev Biol. 2017 Jan 15;421(2):233-244. doi: 10.1016/j.ydbio.2016.11.015. Epub 2016 Nov 28.


Axonal branching is one of the key processes within the enormous complexity of the nervous system to enable a single neuron to send information to multiple targets. However, the molecular mechanisms that control branch formation are poorly understood. In particular, previous studies have rarely addressed the mechanisms underlying axonal bifurcation, in which axons form new branches via splitting of the growth cone. We demonstrate that DISCO Interacting Protein 2 (DIP2) is required for precise axonal bifurcation in Drosophila mushroom body (MB) neurons by suppressing ectopic bifurcation and regulating the guidance of sister axons. We also found that DIP2 localize to the plasma membrane. Domain function analysis revealed that the AMP-synthetase domains of DIP2 are essential for its function, which may involve exerting a catalytic activity that modifies fatty acids. Genetic analysis and subsequent biochemical analysis suggested that DIP2 is involved in the fatty acid metabolization of acyl-CoA. Taken together, our results reveal a function of DIP2 in the developing nervous system and provide a potential functional relationship between fatty acid metabolism and axon morphogenesis.

Keywords: Axonal branching; DIP2; Drosophila; Mushroom body; acyl-CoA.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Axon Guidance*
  • Axons / metabolism*
  • Clone Cells
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism*
  • Fatty Acids / metabolism
  • Lipid Metabolism
  • Models, Biological
  • Mushroom Bodies / innervation*
  • Mushroom Bodies / metabolism*
  • Mutation / genetics
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Protein Domains
  • RNA Interference
  • Sequence Deletion
  • Sequence Homology, Amino Acid


  • Drosophila Proteins
  • Fatty Acids
  • Nerve Tissue Proteins
  • disco-interacting protein 2, Drosophila