UNC-129 regulates the balance between UNC-40 dependent and independent UNC-5 signaling pathways

Nat Neurosci. 2009 Feb;12(2):150-5. doi: 10.1038/nn.2256. Epub 2009 Jan 25.

Abstract

The UNC-5 receptor mediates axon repulsion from UNC-6/netrin through UNC-40 dependent (UNC-5 + UNC-40) and independent (UNC-5 alone) signaling pathways. It has been shown that UNC-40-dependent signaling is required for long-range repulsion of UNC-6/netrin; however, the mechanisms used to regulate distinct UNC-5 signaling pathways are poorly understood. We found that the C. elegans transforming growth factor beta (TGF-beta) family ligand UNC-129, graded opposite to UNC-6/netrin, functions independent of the canonical TGF-beta receptors to regulate UNC-5 cellular responses. Our observations indicates that UNC-129 facilitates long-range repulsive guidance of UNC-6 by enhancing UNC-5 + UNC-40 signaling at the expense of UNC-5 alone signaling through interaction with the UNC-5 receptor. This increases the set point sensitivity of growth cones to UNC-6/netrin as they simultaneously migrated up the UNC-129 gradient and down the UNC-6 gradient. Similar regulatory interactions between oppositely graded extracellular cues may be a common theme in guided cell and axon migrations.

Publication types

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

MeSH terms

  • Animals
  • Axons / physiology
  • COS Cells
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Movement / physiology
  • Chlorocebus aethiops
  • Gene Expression Regulation, Developmental
  • Growth Cones / physiology
  • Mutagenesis
  • Nervous System / cytology
  • Nervous System / embryology*
  • Neurons / physiology
  • Neurons / ultrastructure
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction / physiology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Cell Adhesion Molecules
  • Receptors, Cell Surface
  • Transforming Growth Factor beta
  • UNC-129 protein, C elegans
  • UNC-40 protein, C elegans
  • UNC-5 protein, C elegans