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摘要 : 在胚胎发育过程中,重要的是神经突触要在正确的时间和正确的地点形成。线虫的DD和VD运动神经元就说明了这一点:DD神经元在第一个幼虫阶段发生背-腹重新连线,而VD运动神经元则保持一个不变的神经支配模式,与DD运动神经元的神经支配模式不同。

 在胚胎发育过程中,重要的是神经突触要在正确的时间和正确的地点形成。线虫的DD和VD运动神经元就说明了这一点:DD神经元在第一个幼虫阶段发生背-腹重新连线,而VD运动神经元则保持一个不变的神经支配模式,与DD运动神经元的神经支配模式不同。在这篇论文中,Oliver Hobert及同事发现,三个基因调控因子(UNC-30、LIN-14和UNC-55 DNA-结合蛋白)和它们的目标(OIG-1, 一种以前不知道的细胞外 “突触组织器”蛋白)控制DD和VD神经元的正确的连线和重新连线。这项工作显示了一个“交叉”策略,利用该策略,UNC-30在DD神经元中与通过时间(不是通过空间)控制的LIN-14相互作用,在VD神经元中与通过空间(不是通过时间)控制的UNC-55相互作用。


Spatiotemporal control of a novel synaptic organizer molecule


Synapse formation is a process tightly controlled in space and time. How gene regulatory mechanisms specify spatial and temporal aspects of synapse formation is not well understood. In the nematode Caenorhabditis elegans, two subtypes of the D-type inhibitory motor neuron (MN) classes, the dorsal D (DD) and ventral D (VD) neurons, extend axons along both the dorsal and ventral nerve cords. The embryonically generated DD motor neurons initially innervate ventral muscles in the first (L1) larval stage and receive their synaptic input from cholinergic motor neurons in the dorsal cord. They rewire by the end of the L1 moult to innervate dorsal muscles and to be innervated by newly formed ventral cholinergic motor neurons. VD motor neurons develop after the L1 moult; they take over the innervation of ventral muscles and receive their synaptic input from dorsal cholinergic motor neurons. We show here that the spatiotemporal control of synaptic wiring of the D-type neurons is controlled by an intersectional transcriptional strategy in which the UNC-30 Pitx-type homeodomain transcription factor acts together, in embryonic and early larval stages, with the temporally controlled LIN-14 transcription factor to prevent premature synapse rewiring of the DD motor neurons and, together with the UNC-55 nuclear hormone receptor, to prevent aberrant VD synaptic wiring in later larval and adult stages. A key effector of this intersectional transcription factor combination is a novel synaptic organizer molecule, the single immunoglobulin domain protein OIG-1. OIG-1 is perisynaptically localized along the synaptic outputs of the D-type motor neurons in a temporally controlled manner and is required for appropriate selection of both pre- and post-synaptic partners.

来源: Nature 浏览次数:0


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