title: Wnt4 is a local repulsive cue that determines synaptic target specificity.
abstract: How synaptic specificity is molecularly coded in target cells is a long-standing question in neuroscience. Whereas essential roles of several target-derived attractive cues have been shown, less is known about the role of repulsion by nontarget cells. We conducted single-cell microarray analysis of two neighboring muscles (M12 and M13) in Drosophila, which are innervated by distinct motor neurons, by directly isolating them from dissected embryos. We identified a number of potential target cues that are differentially expressed between the two muscles, including M13-enriched Wnt4. When the functions of Wnt4, or putative receptors Frizzled 2 and Derailed-2 or Dishevelled were inhibited, motor neurons that normally innervate M12 (MN12s) formed smaller synapses on M12 but instead formed ectopic nerve endings on M13. Conversely, ectopic expression of Wnt4 in M12 inhibits synapse formation by MN12s. These results suggest that Wnt4, via Frizzled 2, Derailed-2, and Dishevelled, generates target specificity by preventing synapse formation on a nontarget muscle. Ectopic expression of five other M13-enriched genes, including beat-IIIc and Glutactin, also inhibits synapse formation by MN12s. These results demonstrate an important role for local repulsion in regulating cell-to-cell target specificity.
authors.affiliation: Department of Physics, Graduate School of Science, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Inaki
authors.forename: Shingo
authors.initials: S
authors.lastname: Yoshikawa
authors.forename: John B
authors.initials: JB
authors.lastname: Thomas
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Akinao
authors.initials: A
authors.lastname: Nose
mesh_terms: D000818:Animals; D003463:Cues; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D009132:Muscles / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D006023:Glycoproteins; D012333:RNA, Messenger; D051153:Wnt Proteins; C454442:Wnt4 protein, Drosophila