C-elegans ZAG-1, a Zn-finger-homeodomain protein, regulates axonal development and neuronal differentiation
C-elegans ZAG-1, a Zn-finger-homeodomain protein, regulates axonal development and neuronal differentiation
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DOI：
10.1242/dev.00571
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发表时间：
2003-08-01
期刊：
影响因子：
4.6
通讯作者：
Chiu, C
中科院分区：
文献类型：
--
作者：
Clark, SG;Chiu, C
神经元获得不同的细胞身份，并执行差异基因程序，以产生相应的神经元属性。根据神经元的位置、轴突结构和突触连接性，将线虫的302个神经元分为118类。许多神经元的发育和分化需要基因zag-1，其编码deltaEF 1/ZFH-1锌指同源结构域蛋白。Zag-1突变引起神经元特异性基因的错误表达、阻断定型轴突分支的形成、扰乱神经元迁移并诱导各种轴突导向、成束和分支错误。Zag-1-GFP翻译报告基因在胚胎发生期间在大多数或所有神经元中瞬时表达，并且在第一幼虫阶段期间在选择的神经元中瞬时表达。对zag-1启动子的分析表明，zag-1在神经元和特定肌肉中表达，并且ZAG-1直接抑制其自身的表达。zag-1活性还下调参与5-羟色胺、多巴胺和GABA的合成或再摄取的基因的表达。我们建议，ZAG-1作为一个转录抑制因子，以调节多个，离散的，神经元特异性方面的终末分化，包括细胞迁移，轴突发育和基因表达。
Neurons acquire distinct cell identities and implement differential gene programs to generate their appropriate neuronal attributes. On the basis of position, axonal structure and synaptic connectivity, the 302 neurons of the nematode Ceanorhabditis elegans are divided into 118 classes. The development and differentiation of many neurons require the gene zag-1, which encodes a deltaEF1/ZFH-1 Zn-finger-homeodomain protein. zag-1 mutations cause misexpression of neuron-specific genes, block formation of stereotypic axon branches, perturb neuronal migrations, and induce various axon-guidance, fasciculation and branching errors. A zag-1-GFP translational reporter is expressed transiently in most or all neurons during embryogenesis and in select neurons during the first larval stage. Analysis of the zag-1 promoter reveals that zag-1 is expressed in neurons and specific muscles, and that ZAG-1 directly represses its own expression. zag-1 activity also downregulates; expression of genes involved in either the synthesis or reuptake of serotonin, dopamine and GABA. We propose that ZAG-1 acts as a transcriptional repressor to regulate multiple, discrete, neuron-specific aspects of terminal differentiation, including cell migration, axonal development and gene expression.