The homeobox transcription factor even-skipped regulates netrin-receptor expression to control dorsal motor-axon projections in Drosophila

Curr Biol. 2005 Aug 9;15(15):1413-9. doi: 10.1016/j.cub.2005.06.058.

Abstract

Homeobox transcription-factor codes control motor-neuron subtype identity and dorsal versus ventral axon guidance in both vertebrate and invertebrate nervous systems; however, the specific axon guidance-receptors that are regulated by these transcription factors to control pathfinding are poorly defined. In Drosophila, the Even-skipped (Eve) transcription factor specifies dorsal motor-axon projection through the regulation of unidentified guidance molecules. The Netrins and their attractive and repulsive receptors DCC and Unc-5, respectively, define important conserved cue and receptor families that control growth-cone guidance. In Drosophila, the Netrins and frazzled (the fly homolog of DCC) contribute to motor-axon guidance. Here, using genetics and single-cell mRNA-expression analysis, we show that expression and requirement of different Netrin receptor combinations correlate with distinct dorsal and ventral motor-axon projections in Drosophila. Mis-expression of eve dorsalizes ventral axons in part through the upregulation of Unc-5, whereas loss of eve function in two dorsally projecting motor neurons results in aberrant axon projections and a failure to express Unc-5. Our results support a functional link between the expression of distinct Netrin receptor combinations and the transcriptional control of dorsal motor-axon guidance.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Drosophila
  • Drosophila Proteins / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Green Fluorescent Proteins
  • Growth Cones / metabolism*
  • Growth Cones / physiology
  • Homeodomain Proteins / metabolism*
  • Immunohistochemistry
  • Motor Neurons / metabolism
  • Motor Neurons / physiology*
  • Netrin Receptors
  • Receptors, Cell Surface / metabolism*
  • Transcription Factors / metabolism*

Substances

  • Drosophila Proteins
  • Homeodomain Proteins
  • Netrin Receptors
  • Receptors, Cell Surface
  • Transcription Factors
  • eve protein, Drosophila
  • fra protein, Drosophila
  • Green Fluorescent Proteins