Transcriptional regulation and stabilization of left-right neuronal identity in C. elegans
Transcriptional regulation and stabilization of left-right neuronal identity in C. elegans
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DOI：
10.1101/gad.1763509
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发表时间：
2009-02-01
影响因子：
10.5
通讯作者：
Bargmann, Cornelia I.
中科院分区：
文献类型：
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作者：
Lesch, Bluma J.;Gehrke, Andrew R.;Bargmann, Cornelia I.
在发育过程中的离散点，瞬时信号被转化为持久的细胞命运。例如，两个称为AWC（ON）和AWC（OFF）的秀丽隐杆线虫嗅觉神经元的不对称身份是由胚胎信号传导途径指定的，但在动物的整个生命中保持不变。在这里，我们表明，DNA结合蛋白NSY-7的行为转换为一个稳定的AWC（ON）身份的短暂的，部分分化的状态。AWC（ON）标记物的表达在nsy-7功能丧失突变体中开始，但随后丢失，因此大多数成年动物具有两个AWC（OFF）神经元而没有AWC（ON）神经元。NSY-7编码与同源结构域具有远距离相似性的蛋白质。它在AWC（ON）中表达，并且是指定AWC（ON）和AWC（OFF）的胚胎信号通路的早期转录靶点;其表达预期未来的AWC不对称性。NSY-7蛋白结合通过8聚体DNA序列的完整生物化学调查鉴定的特定最佳DNA序列。该序列存在于AWC（OFF）标志物的启动子中，并且对于其不对称表达是必需的。AWC（OFF）表达所需的11个碱基对（bp）序列具有两种活性：一个区域激活两个AWC中的表达，重叠的NSY-7结合位点抑制AWC（ON）中的表达。我们的研究结果表明，NSY-7通过抑制AWC（ON）中的AWC（OFF）基因来响应瞬时胚胎信号，从而作为随机指定神经元身份的转录选择器。
At discrete points in development, transient signals are transformed into long-lasting cell fates. For example, the asymmetric identities of two Caenorhabditis elegans olfactory neurons called AWC(ON) and AWC(OFF) are specified by an embryonic signaling pathway, but maintained throughout the life of an animal. Here we show that the DNA-binding protein NSY-7 acts to convert a transient, partially differentiated state into a stable AWC(ON) identity. Expression of an AWC(ON) marker is initiated in nsy-7 loss-of-function mutants, but subsequently lost, so that most adult animals have two AWC(OFF) neurons and no AWC(ON) neurons. nsy-7 encodes a protein with distant similarity to a homeodomain. It is expressed in AWC(ON), and is an early transcriptional target of the embryonic signaling pathway that specifies AWC(ON) and AWC(OFF); its expression anticipates future AWC asymmetry. The NSY-7 protein binds a specific optimal DNA sequence that was identified through a complete biochemical survey of 8-mer DNA sequences. This sequence is present in the promoter of an AWC(OFF) marker and essential for its asymmetric expression. An 11-base-pair ( bp) sequence required for AWC(OFF) expression has two activities: One region activates expression in both AWCs, and the overlapping NSY-7-binding site inhibits expression in AWC(ON). Our results suggest that NSY-7 responds to transient embryonic signaling by repressing AWC(OFF) genes in AWC(ON), thus acting as a transcriptional selector for a randomly specified neuronal identity.