Rac GTPases control axon growth, guidance and branching

Nature. 2002 Mar 28;416(6879):442-7. doi: 10.1038/416442a.


Growth, guidance and branching of axons are all essential processes for the precise wiring of the nervous system. Rho family GTPases transduce extracellular signals to regulate the actin cytoskeleton. In particular, Rac has been implicated in axon growth and guidance. Here we analyse the loss-of-function phenotypes of three Rac GTPases in Drosophila mushroom body neurons. We show that progressive loss of combined Rac1, Rac2 and Mtl activity leads first to defects in axon branching, then guidance, and finally growth. Expression of a Rac1 effector domain mutant that does not bind Pak rescues growth, partially rescues guidance, but does not rescue branching defects of Rac mutant neurons. Mosaic analysis reveals both cell autonomous and non-autonomous functions for Rac GTPases, the latter manifesting itself as a strong community effect in axon guidance and branching. These results demonstrate the central role of Rac GTPases in multiple aspects of axon development in vivo, and suggest that axon growth, guidance and branching could be controlled by differential activation of Rac signalling pathways.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Axons / enzymology
  • Axons / physiology*
  • Cell Division
  • Cell Movement
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Genes, Insect
  • Molecular Sequence Data
  • Mutation
  • RAC2 GTP-Binding Protein
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / physiology*
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / physiology*


  • Drosophila Proteins
  • rac GTP-Binding Proteins
  • rac1 GTP-Binding Protein