Wnt signaling positions neuromuscular connectivity by inhibiting synapse formation in C. elegans

Cell. 2007 Aug 24;130(4):704-16. doi: 10.1016/j.cell.2007.06.046.

Abstract

Nervous system function is mediated by a precisely patterned network of synaptic connections. While several cell-adhesion and secreted molecules promote the assembly of synapses, the contribution of signals that negatively regulate synaptogenesis is not well understood. We examined synapse formation in the Caenorhabditis elegans motor neuron DA9, whose presynapses are restricted to a specific segment of its axon. We report that the Wnt lin-44 localizes the Wnt receptor lin-17/Frizzled (Fz) to a subdomain of the DA9 axon that is devoid of presynaptic specializations. When this signaling pathway, composed of the Wnts lin-44 and egl-20, lin-17/Frizzled and dsh-1/Dishevelled, is compromised, synapses develop ectopically in this subdomain. Conversely, overexpression of LIN-44 in cells adjacent to DA9 is sufficient to expand LIN-17 localization within the DA9 axon, thereby inhibiting presynaptic assembly. These results suggest that morphogenetic signals can spatially regulate the patterning of synaptic connections by subdividing an axon into discrete domains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology
  • Body Patterning
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / isolation & purification
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans* / anatomy & histology
  • Caenorhabditis elegans* / embryology
  • Caenorhabditis elegans* / genetics
  • Caenorhabditis elegans* / growth & development
  • Caenorhabditis elegans* / physiology
  • Embryo, Nonmammalian
  • Frizzled Receptors / genetics
  • Frizzled Receptors / metabolism
  • Motor Neurons / physiology
  • Neuromuscular Junction / physiology*
  • Presynaptic Terminals / physiology
  • Signal Transduction*
  • Synapses / physiology*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Frizzled Receptors
  • Wnt Proteins