Drosophila motor neuron retraction during metamorphosis is mediated by inputs from TGF-β/BMP signaling and orphan nuclear receptors.
Drosophila motor neuron retraction during metamorphosis is mediated by inputs from TGF-β/BMP signaling and orphan nuclear receptors.
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DOI：
10.1371/journal.pone.0040255
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dura JM
中科院分区：
文献类型：
--
作者：
Boulanger A;Farge M;Ramanoudjame C;Wharton K;Dura JM
幼虫运动神经元在果蝇变态神经肌肉接头拆除过程中重塑。在这项研究中，我们基于 β-血影蛋白的早期消失和微管蛋白的持续存在来描述运动神经元的回缩，而不是退化。通过用显性失活形式的 Dynamin 阻断细胞动力学，我们发现吞噬细胞在此过程中发挥着关键作用。重要的是，我们显示了靠近神经肌肉接头的外周胶质细胞的存在，该接头在运动神经元之前缩回。我们还表明，在肌肉中，编码突触后解体所需的类固醇激素受体的 EcR-B1 的表达受到 ftz-f1/Hr39 孤儿核受体通路的控制，但不受 TGF-β 信号通路的控制。在运动神经元中，两条平行通路（TGF-β 信号传导和核受体）激活 EcR-B1 表达会触发轴突收缩。我们提出来自 TGF-β 家族配体的信号由拆卸肌（突触后区室）产生并由运动神经元（突触前区室）接收，导致运动神经元回缩。运动神经元中两条通路的要求为突触后降解对运动神经元回缩的指导作用提供了分子解释。这种机制确保了两个过程的暂时性，并防止运动神经元在突触后退化之前修剪。
Larval motor neurons remodel during Drosophila neuro-muscular junction dismantling at metamorphosis. In this study, we describe the motor neuron retraction as opposed to degeneration based on the early disappearance of β-Spectrin and the continuing presence of Tubulin. By blocking cell dynamics with a dominant-negative form of Dynamin, we show that phagocytes have a key role in this process. Importantly, we show the presence of peripheral glial cells close to the neuro-muscular junction that retracts before the motor neuron. We show also that in muscle, expression of EcR-B1 encoding the steroid hormone receptor required for postsynaptic dismantling, is under the control of the ftz-f1/Hr39 orphan nuclear receptor pathway but not the TGF-β signaling pathway. In the motor neuron, activation of EcR-B1 expression by the two parallel pathways (TGF-β signaling and nuclear receptor) triggers axon retraction. We propose that a signal from a TGF-β family ligand is produced by the dismantling muscle (postsynapse compartment) and received by the motor neuron (presynaptic compartment) resulting in motor neuron retraction. The requirement of the two pathways in the motor neuron provides a molecular explanation for the instructive role of the postsynapse degradation on motor neuron retraction. This mechanism insures the temporality of the two processes and prevents motor neuron pruning before postsynaptic degradation.
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