Regulation of central neuron synaptic targeting by the Drosophila POU protein, Acj6.
Regulation of central neuron synaptic targeting by the Drosophila POU protein, Acj6.
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DOI：
10.1242/dev.127.11.2395
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发表时间：
2000-06
期刊：
影响因子：
4.6
通讯作者：
S. Certel;P. Clyne;J. Carlson;W. A. Johnson
中科院分区：
文献类型：
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作者：
S. Certel;P. Clyne;J. Carlson;W. A. Johnson
果蝇IV类POU结构域基因异常化学感觉跳跃6（acj6）的突变先前已被证明会导致气味敏感性的生理缺陷。然而，Acj6功能的丧失也对协调的幼虫和成虫运动产生严重的不利影响，这不能用气味检测的简单丧失来解释。除了嗅觉感觉神经元外，Acj6在从胚胎晚期到成体阶段的中枢神经系统中的有丝分裂后中间神经元的一个不同子集中表达。在幼虫和成虫脑中，Acj6在中枢脑、视叶和触角叶神经元中高度表达。幼虫视叶神经元中Acj6功能的丧失导致视网膜轴突靶向和突触选择紊乱。此外，在acj6突变蛹脑的髓质中，板层神经元本身表现出紊乱的突触乔木，这表明Acj6可能在调节突触连接或结构中发挥作用。为了进一步验证这一假设，我们在运动神经元中错误表达了两种Acj6亚型，这两种Acj6亚型是由选择性剪接的acj6转录本产生的，导致氨基末端POU IV盒的显著结构差异。Acj6的错误表达引起神经肌肉接头的显著改变，与特定Acj6亚型相关的神经末梢分支和突触形成的对比效应。我们的研究结果表明，IV类POU结构域因子，Acj6，可能发挥重要作用，调节中枢神经元的突触靶选择和氨基末端POU IV盒是重要的调节Acj6活性。
Mutations in the Drosophila class IV POU domain gene, abnormal chemosensory jump 6 (acj6), have previously been shown to cause physiological deficits in odor sensitivity. However, loss of Acj6 function also has a severe detrimental effect upon coordinated larval and adult movement that cannot be explained by the simple loss in odorant detection. In addition to olfactory sensory neurons, Acj6 is expressed in a distinct subset of postmitotic interneurons in the central nervous system from late embryonic to adult stages. In the larval and adult brain, Acj6 is highly expressed in central brain, optic and antennal lobe neurons. Loss of Acj6 function in larval optic lobe neurons results in disorganized retinal axon targeting and synapse selection. Furthermore, the lamina neurons themselves exhibit disorganized synaptic arbors in the medulla of acj6 mutant pupal brains, suggesting that Acj6 may play a role in regulating synaptic connections or structure. To further test this hypothesis, we misexpressed two Acj6 isoforms in motor neurons where they are not normally found. The two Acj6 isoforms are produced from alternatively spliced acj6 transcripts, resulting in significant structural differences in the amino-terminal POU IV box. Acj6 misexpression caused marked alterations at the neuromuscular junction, with contrasting effects upon nerve terminal branching and synapse formation associated with specific Acj6 isoforms. Our results suggest that the class IV POU domain factor, Acj6, may play an important role in regulating synaptic target selection by central neurons and that the amino-terminal POU IV box is important for regulation of Acj6 activity.