Wnt4 is a local repulsive cue that determines synaptic target specificity
Wnt4 is a local repulsive cue that determines synaptic target specificity
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DOI：
10.1016/j.cub.2007.08.013
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发表时间：
2007-09-18
期刊：
影响因子：
9.2
通讯作者：
Nose, Akinao
中科院分区：
文献类型：
--
作者：
Inaki, Mikiko;Yoshikawa, Shingo;Nose, Akinao
突触特异性如何在靶细胞中进行分子编码是神经科学中一个长期存在的问题。尽管已经显示了几种靶细胞衍生的吸引线索的重要作用，但对非靶细胞的排斥作用知之甚少[1-3]。我们进行了两个相邻的肌肉（M12和M13）在果蝇，这是由不同的运动神经元支配的单细胞微阵列分析，通过直接分离它们从解剖胚胎。我们确定了一些在两种肌肉之间差异表达的潜在目标线索，包括富含M13的Wnt 4。当Wnt 4或假定的受体Frizzled 2和Derailed-2或Dishevelled的功能被抑制时，通常支配M12的运动神经元（MN 12）在M12上形成较小的突触，但在M13上形成异位神经末梢。相反，M12中Wnt 4的异位表达抑制MN 12的突触形成。这些结果表明，Wnt 4通过Frizzled 2，Derailed-2和Dishevelled，通过阻止非靶肌肉上的突触形成来产生靶特异性。其他五个富含M13的基因的异位表达，包括beat-IIIc和Glucoprins，也抑制了MN 12的突触形成。这些结果证明了局部排斥在调节细胞对细胞靶向特异性中的重要作用。
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 [1-3]. 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.