{"title":"当转录因子水平因核输出和降解而急剧下降时,目标基因的反应也不同。","authors":"James McGehee, Angelike Stathopoulos","doi":"10.1242/dev.202775","DOIUrl":null,"url":null,"abstract":"<p><p>Defining the time of action for morphogens requires tools capable of temporally controlled perturbations. To study how the transcription factor Dorsal affects patterning of the Drosophila embryonic dorsal-ventral axis, we used two light-inducible tags that trigger either nuclear export or degradation of Dorsal under blue light. Nuclear export of Dorsal leads to loss of the high-threshold, ventrally expressed target gene snail (sna), while the low-threshold, laterally expressed target gene short-gastrulation (sog) is retained. In contrast, degradation of Dorsal results in retention of sna, loss of sog, and lower nuclear levels compared to when Dorsal is exported from the nucleus. To understand why nuclear export causes loss of sna but degradation does not, we investigated Dorsal kinetics using photobleaching and found that it rapidly re-enters the nucleus even under blue-light conditions favoring export. The associated kinetics of Dorsal being rapidly imported and exported continuously are likely responsible for loss of sna but, alternatively, can support sog. Collectively, our results indicate that this dynamic patterning process is influenced by both Dorsal concentration and nuclear retention.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Target gene responses differ when transcription factor levels are acutely decreased by nuclear export versus degradation.\",\"authors\":\"James McGehee, Angelike Stathopoulos\",\"doi\":\"10.1242/dev.202775\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Defining the time of action for morphogens requires tools capable of temporally controlled perturbations. To study how the transcription factor Dorsal affects patterning of the Drosophila embryonic dorsal-ventral axis, we used two light-inducible tags that trigger either nuclear export or degradation of Dorsal under blue light. Nuclear export of Dorsal leads to loss of the high-threshold, ventrally expressed target gene snail (sna), while the low-threshold, laterally expressed target gene short-gastrulation (sog) is retained. In contrast, degradation of Dorsal results in retention of sna, loss of sog, and lower nuclear levels compared to when Dorsal is exported from the nucleus. To understand why nuclear export causes loss of sna but degradation does not, we investigated Dorsal kinetics using photobleaching and found that it rapidly re-enters the nucleus even under blue-light conditions favoring export. The associated kinetics of Dorsal being rapidly imported and exported continuously are likely responsible for loss of sna but, alternatively, can support sog. Collectively, our results indicate that this dynamic patterning process is influenced by both Dorsal concentration and nuclear retention.</p>\",\"PeriodicalId\":11375,\"journal\":{\"name\":\"Development\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Development\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1242/dev.202775\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/8 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"DEVELOPMENTAL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Development","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1242/dev.202775","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/8 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
确定形态发生因子的作用时间需要能够进行时间控制扰动的工具。为了研究转录因子 Dorsal 如何影响果蝇胚胎背-腹轴的模式化,我们使用了两种光诱导标签,在蓝光下触发 Dorsal 的核输出或降解。Dorsal 的核输出导致高阈值、腹侧表达的目标基因 snail(sna)丢失,而低阈值、侧向表达的目标基因 short-gastrulation (sog)得以保留。相反,与 Dorsal 从细胞核中导出时相比,Dorsal 降解会导致 sna 保留、sog 丢失以及核水平降低。为了理解为什么核输出会导致 sna 丢失而降解不会,我们利用光漂白技术研究了 Dorsal 的动力学,发现即使在有利于 Dorsal 输出的蓝光条件下,它也会迅速重新进入细胞核。Dorsal 快速输入和持续输出的相关动力学可能是导致 sna 丢失的原因,但也可能支持 sog。总之,我们的研究结果表明,这种动态模式化过程受到 Dorsal 浓度和核保留的影响。
Target gene responses differ when transcription factor levels are acutely decreased by nuclear export versus degradation.
Defining the time of action for morphogens requires tools capable of temporally controlled perturbations. To study how the transcription factor Dorsal affects patterning of the Drosophila embryonic dorsal-ventral axis, we used two light-inducible tags that trigger either nuclear export or degradation of Dorsal under blue light. Nuclear export of Dorsal leads to loss of the high-threshold, ventrally expressed target gene snail (sna), while the low-threshold, laterally expressed target gene short-gastrulation (sog) is retained. In contrast, degradation of Dorsal results in retention of sna, loss of sog, and lower nuclear levels compared to when Dorsal is exported from the nucleus. To understand why nuclear export causes loss of sna but degradation does not, we investigated Dorsal kinetics using photobleaching and found that it rapidly re-enters the nucleus even under blue-light conditions favoring export. The associated kinetics of Dorsal being rapidly imported and exported continuously are likely responsible for loss of sna but, alternatively, can support sog. Collectively, our results indicate that this dynamic patterning process is influenced by both Dorsal concentration and nuclear retention.
期刊介绍:
Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community.
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