Lesch Bluma J, Gehrke Andrew R, Bulyk Martha L, Bargmann Cornelia I
Laboratory of Neural Circuits and Behavior, Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA.
Genes Dev. 2009 Feb 1;23(3):345-58. doi: 10.1101/gad.1763509.
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.
在发育的离散点上，瞬时信号会转化为持久的细胞命运。例如，秀丽隐杆线虫的两个嗅觉神经元AWC(ON)和AWC(OFF)的不对称身份由一条胚胎信号通路指定，并在动物的整个生命周期中得以维持。在这里，我们表明DNA结合蛋白NSY-7的作用是将瞬时的、部分分化的状态转化为稳定的AWC(ON)身份。在nsy-7功能缺失突变体中启动了AWC(ON)标记的表达，但随后丢失，因此大多数成年动物有两个AWC(OFF)神经元，而没有AWC(ON)神经元。nsy-7编码一种与同源结构域有远缘相似性的蛋白质。它在AWC(ON)中表达，是指定AWC(ON)和AWC(OFF)的胚胎信号通路的早期转录靶点；其表达预示着未来的AWC不对称性。NSY-7蛋白结合通过对8聚体DNA序列进行完整生化筛选鉴定出的特定最佳DNA序列。该序列存在于AWC(OFF)标记的启动子中，对其不对称表达至关重要。AWC(OFF)表达所需的11个碱基对（bp）序列具有两种活性：一个区域在两个AWC中均激活表达，而重叠的NSY-7结合位点抑制AWC(ON)中的表达。我们的结果表明，NSY-7通过在AWC(ON)中抑制AWC(OFF)基因来响应瞬时胚胎信号，从而作为随机指定的神经元身份的转录选择器。
