An RNAi-based approach identifies molecules required for glutamatergic and GABAergic synapse development
An RNAi-based approach identifies molecules required for glutamatergic and GABAergic synapse development
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DOI：
10.1016/j.neuron.2006.12.012
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发表时间：
2007-01-18
期刊：
影响因子：
16.2
通讯作者：
Greenberg, Michael E.
中科院分区：
文献类型：
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作者：
Paradis, Suzanne;Harrar, Dana B.;Greenberg, Michael E.
我们报告了基因筛查的结果，以确定对突触形成和/或维持至关重要的分子。用siRNAs降低神经元中候选基因的表达，并评估突触发育。我们调查了22个钙粘素家族成员，展示了钙粘蛋白-11和钙粘蛋白-13在突触发育中的不同作用。我们的屏幕还显示了4类信号素Sema4B和Sema4D在谷氨酸和/或GABA能突触发育中的作用。我们发现Sema4D影响GABA能突触的形成，但不影响谷氨酸能突触的形成。我们的筛查还发现，活性调节的小GTP酶Rem2是突触发育的调节因子。已知的钙通道调节剂Rem2可能是控制突触数量的动态平衡机制的一部分。这些实验确定了RNAi筛选的可行性，以表征控制哺乳动物神经元发育的机制，并确定调节突触形成和/或维持的遗传程序的组件。
We report the results of a genetic screen to identify molecules important for synapse formation and/or maintenance. siRNAs were used to decrease the expression of candidate genes in neurons, and synapse development was assessed. We surveyed 22 cadherin family members and demonstrated distinct roles for cadherin-11 and cadherin-13 in synapse development. Our screen also revealed roles for the class 4 Semaphorins Sema4B and Sema4D in the development of glutamatergic and/or GABAergic synapses. We found that Sema4D affects the formation of GABAergic, but not glutamatergic, synapses. Our screen also identified the activity-regulated small GTPase Rem2 as a regulator of synapse development. A known calcium channel modulator, Rem2 may function as part of a homeostatic mechanism that controls synapse number. These experiments establish the feasibility of RNAi screens to characterize the mechanisms that control mammalian neuronal development and to identify components of the genetic program that regulate synapse formation and/or maintenance.