MADD-4 is a secreted cue required for midline-oriented guidance in Caenorhabditis elegans

Dev Cell. 2011 Oct 18;21(4):669-80. doi: 10.1016/j.devcel.2011.07.020.

Abstract

The netrins and slits are two families of widely conserved cues that guide axons and cells along the dorsal-ventral (D-V) axis of animals. These cues typically emanate from the dorsal or ventral midlines and provide spatial information to migrating cells by forming gradients along the D-V axis. Some cell types, however, extend processes to both the dorsal and ventral midlines, suggesting the existence of additional guidance cues that are secreted from both midlines. Here, we report that a previously uncharacterized protein called MADD-4 is secreted by the dorsal and ventral nerve cords of the nematode C. elegans to attract sensory axons and muscle membrane extensions called muscle arms. MADD-4's activity is dependent on UNC-40/DCC, a netrin receptor, which functions cell-autonomously to direct membrane extension. The biological role of MADD-4 orthologs, including ADAMTSL1 and 3 in mammals, is unknown. MADD-4 may therefore represent the founding member of a family of guidance proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAMTS Proteins
  • Animals
  • Animals, Genetically Modified
  • Axons / metabolism
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Adhesion Molecules / metabolism
  • Cell Movement
  • Cues*
  • Extracellular Matrix Proteins / metabolism
  • Gene Expression Regulation, Developmental
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism
  • Humans
  • Motor Neurons / cytology
  • Motor Neurons / metabolism*
  • Muscles / cytology
  • Muscles / metabolism
  • Mutation / genetics*
  • Nerve Tissue / cytology
  • Nerve Tissue / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Netrin Receptors
  • Promoter Regions, Genetic / genetics
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism

Substances

  • ADAMTSL1 protein, human
  • ADAMTSL3 protein, human
  • Caenorhabditis elegans Proteins
  • Cell Adhesion Molecules
  • Extracellular Matrix Proteins
  • Guanine Nucleotide Exchange Factors
  • MADD-4 protein, C elegans
  • Nerve Tissue Proteins
  • Netrin Receptors
  • Receptors, Cell Surface
  • UNC-40 protein, C elegans
  • ADAMTS Proteins