Mutual inhibition among postmitotic neurons regulates robustness of brain wiring in Drosophila

Elife. 2013 Mar 5;2:e00337. doi: 10.7554/eLife.00337.

Abstract

Brain connectivity maps display a delicate balance between individual variation and stereotypy, suggesting the existence of dedicated mechanisms that simultaneously permit and limit individual variation. We show that during the development of the Drosophila central nervous system, mutual inhibition among groups of neighboring postmitotic neurons during development regulates the robustness of axon target choice in a nondeterministic neuronal circuit. Specifically, neighboring postmitotic neurons communicate through Notch signaling during axonal targeting, to ensure balanced alternative axon target choices without a corresponding change in cell fate. Loss of Notch in postmitotic neurons modulates an axon's target choice. However, because neighboring axons respond by choosing the complementary target, the stereotyped connectivity pattern is preserved. In contrast, loss of Notch in clones of neighboring postmitotic neurons results in erroneous coinnervation by multiple axons. Our observations establish mutual inhibition of axonal target choice as a robustness mechanism for brain wiring and unveil a novel cell fate independent function for canonical Notch signaling. DOI:http://dx.doi.org/10.7554/eLife.00337.001.

Keywords: Axonal targeting; D. melanogaster; Neural Circuit; Neurobiology; Notch Signaling; Robustness; Variability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology
  • Brain / metabolism
  • Brain / physiology*
  • Cell Line
  • Computer Simulation
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mitosis*
  • Models, Biological
  • Neural Inhibition*
  • Neurons / metabolism
  • Neurons / physiology*
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism
  • Signal Transduction
  • Time Factors
  • Transfection
  • Visual Pathways / metabolism
  • Visual Pathways / physiology*
  • p21-Activated Kinases / metabolism

Substances

  • Drosophila Proteins
  • N protein, Drosophila
  • Receptors, Notch
  • Pak protein, Drosophila
  • p21-Activated Kinases
  • JNK Mitogen-Activated Protein Kinases

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.