Packard Mary, Koo Ellen Sumin, Gorczyca Michael, Sharpe Jade, Cumberledge Susan, Budnik Vivian
Department of Biology, University of Massachusetts, Amherst, MA 01003, USA.
Cell. 2002 Nov 1;111(3):319-30. doi: 10.1016/s0092-8674(02)01047-4.
At vertebrate neuromuscular junctions (NMJs), Agrin plays pivotal roles in synapse development, but molecules that activate synapse formation at central synapses are largely unknown. Members of the Wnt family are well established as morphogens, yet recently they have also been implicated in synapse maturation. Here we demonstrate that the Drosophila Wnt, Wingless (Wg), is essential for synapse development. We show that Wg and its receptor are expressed at glutamatergic NMJs, and that Wg is secreted by synaptic boutons. Loss of Wg leads to dramatic reductions in target-dependent synapse formation, and new boutons either fail to develop active zones and postsynaptic specializations or these are strikingly aberrant. We suggest that Wg signals the coordinated development of pre- and postsynaptic compartments.
在脊椎动物神经肌肉接头(NMJ)中,聚集蛋白在突触发育中起关键作用,但激活中枢突触形成的分子在很大程度上尚不清楚。Wnt家族成员作为形态发生素已被充分确立,然而最近它们也与突触成熟有关。在这里,我们证明果蝇的Wnt,无翅(Wg),对突触发育至关重要。我们表明Wg及其受体在谷氨酸能NMJ处表达,并且Wg由突触小体分泌。Wg的缺失导致靶标依赖性突触形成显著减少,新的突触小体要么无法形成活性区和突触后特化结构,要么这些结构明显异常。我们认为Wg为突触前和突触后区室的协调发育提供信号。