A transcription factor network coordinates attraction, repulsion, and adhesion combinatorially to control motor axon pathway selection

Neuron. 2014 Mar 19;81(6):1297-1311. doi: 10.1016/j.neuron.2014.01.038. Epub 2014 Feb 20.


Combinations of transcription factors (TFs) instruct precise wiring patterns in the developing nervous system; however, how these factors impinge on surface molecules that control guidance decisions is poorly understood. Using mRNA profiling, we identified the complement of membrane molecules regulated by the homeobox TF Even-skipped (Eve), the major determinant of dorsal motor neuron (dMN) identity in Drosophila. Combinatorial loss- and gain-of-function genetic analyses of Eve target genes indicate that the integrated actions of attractive, repulsive, and adhesive molecules direct eve-dependent dMN axon guidance. Furthermore, combined misexpression of Eve target genes is sufficient to partially restore CNS exit and can convert the guidance behavior of interneurons to that of dMNs. Finally, we show that a network of TFs, comprised of eve, zfh1, and grain, induces the expression of the Unc5 and Beaten-path guidance receptors and the Fasciclin 2 and Neuroglian adhesion molecules to guide individual dMN axons.

Publication types

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

MeSH terms

  • Animals
  • Axons / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology
  • Interneurons / metabolism
  • Motor Neurons / metabolism*
  • Nerve Net / growth & development
  • Nerve Net / metabolism*
  • Signal Transduction
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Drosophila Proteins
  • Transcription Factors