Wnt signals organize synaptic prepattern and axon guidance through the zebrafish unplugged/MuSK receptor

Neuron. 2009 Mar 12;61(5):721-33. doi: 10.1016/j.neuron.2008.12.025.


Early during neuromuscular development, acetylcholine receptors (AChRs) accumulate at the center of muscle fibers, precisely where motor growth cones navigate and synapses eventually form. Here, we show that Wnt11r binds to the zebrafish unplugged/MuSK ectodomain to organize this central muscle zone. In the absence of such a zone, prepatterned AChRs fail to aggregate and, as visualized by live-cell imaging, growth cones stray from their central path. Using inducible unplugged/MuSK transgenes, we show that organization of the central muscle zone is dispensable for the formation of neural synapses, but essential for AChR prepattern and motor growth cone guidance. Finally, we show that blocking noncanonical dishevelled signaling in muscle fibers disrupts AChR prepatterning and growth cone guidance. We propose that Wnt ligands activate unplugged/MuSK signaling in muscle fibers to restrict growth cone guidance and AChR prepatterns to the muscle center through a mechanism reminiscent of the planar cell polarity pathway.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Axons / physiology*
  • Body Patterning / physiology
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Developmental / physiology
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Hot Temperature
  • Immunoprecipitation / methods
  • RNA, Messenger / metabolism
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Signal Transduction / genetics*
  • Synapses / physiology*
  • Transfection / methods
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Zebrafish / genetics
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*
  • Zebrafish Proteins / physiology*


  • Homeodomain Proteins
  • MuSK protein, zebrafish
  • RNA, Messenger
  • Wnt Proteins
  • Zebrafish Proteins
  • Receptor Protein-Tyrosine Kinases