Burmeister Sabrina S, Fernald Russell D
Department of Biological Sciences, Stanford University, Stanford, California 94305, USA.
J Comp Neurol. 2005 Jan 10;481(2):220-32. doi: 10.1002/cne.20380.
Immediate-early gene expression is a key part of a neuron's response to behaviorally relevant stimuli and, as a result, localization of immediate-early gene expression can be a useful marker for neural activity. We characterized the immediate-early gene egr-1 (also called zif268, NGFI-A, krox-24, ZENK) in the teleost Astatotilapia (Haplochromis) burtoni. We compared the A. burtoni egr-1 predicted protein sequence to that of other vertebrates, characterized its gene expression time course, and localized its induced expression throughout the brain. The A. burtoni egr-1 predicted protein shared putative functional domains with egr-1 of other vertebrates and shared 81% sequence similarity with zebrafish and 66% with mouse. We identified distinct mammalian and teleost inserts rich in serine residues within one activation domain, suggesting convergent responses to selection pressures to increase the number of serine residues in this region. Functionally, we found that A. burtoni egr-1 gene expression peaked near 30 minutes after pharmacological stimulation and thereby displayed the transient expression above basal levels characteristic of egr-1 expression in birds and mammals. Finally, we observed distinct patterns of egr-1 gene induction in the brain by natural and pharmacological stimuli. Unstimulated males had very low expression levels of egr-1, whereas males stimulated by their normal environment showed higher levels of expression specific to particular brain regions. Males injected with a glutamate receptor agonist also had region-specific induction of egr-1 expression. We conclude that the egr-1 immediate-early gene response is evolutionarily conserved and will, therefore, be useful for identifying functional neural responses in nontraditional model species.
即刻早期基因表达是神经元对行为相关刺激作出反应的关键部分,因此,即刻早期基因表达的定位可作为神经活动的有用标记。我们对硬骨鱼伯氏妊丽鱼(Astatotilapia (Haplochromis) burtoni)中的即刻早期基因egr-1(也称为zif268、NGFI-A、krox-24、ZENK)进行了表征。我们将伯氏妊丽鱼egr-1预测的蛋白质序列与其他脊椎动物的进行了比较,确定了其基因表达的时间进程,并在整个大脑中定位了其诱导表达。伯氏妊丽鱼egr-1预测的蛋白质与其他脊椎动物的egr-1共享推定的功能域,与斑马鱼的序列相似性为81%,与小鼠的为66%。我们在一个激活域内鉴定出富含丝氨酸残基的独特的哺乳动物和硬骨鱼插入片段,这表明在增加该区域丝氨酸残基数量的选择压力下存在趋同反应。在功能上,我们发现伯氏妊丽鱼egr-1基因表达在药理学刺激后约30分钟达到峰值,从而表现出高于鸟类和哺乳动物中egr-1表达基础水平的瞬时表达特征。最后,我们观察到自然和药理学刺激在大脑中诱导egr-1基因的不同模式。未受刺激的雄性egr-1表达水平非常低,而受到正常环境刺激的雄性则在特定脑区表现出较高的表达水平。注射谷氨酸受体激动剂的雄性也有egr-1表达的区域特异性诱导。我们得出结论,egr-1即刻早期基因反应在进化上是保守的,因此将有助于识别非传统模型物种中的功能性神经反应。