Frøland Steindal Inga A, Beale Andrew D, Yamamoto Yoshiyuki, Whitmore David
Department of Cell and Developmental Biology, University College London, 21 University Street, London WC1E 6DE, UK.
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Dev Biol. 2018 Sep 15;441(2):345-354. doi: 10.1016/j.ydbio.2018.06.008. Epub 2018 Jun 23.
Most animals and plants live on the planet exposed to periods of rhythmic light and dark. As such, they have evolved endogenous circadian clocks to regulate their physiology rhythmically, and non-visual light detection mechanisms to set the clock to the environmental light-dark cycle. In the case of fish, circadian pacemakers are not only present in the majority of tissues and cells, but these tissues are themselves directly light-sensitive, expressing a wide range of opsin photopigments. This broad non-visual light sensitivity exists to set the clock, but also impacts a wide range of fundamental cell biological processes, such as DNA repair regulation. In this context, Astyanax mexicanus is a very intriguing model system with which to explore non-visual light detection and circadian clock function. Previous work has shown that surface fish possess the same directly light entrainable circadian clocks, described above. The same is true for cave strains of Astyanax in the laboratory, though no daily rhythms have been observed under natural dark conditions in Mexico. There are, however, clear alterations in the cave strain light response and changes to the circadian clock, with a difference in phase of peak gene expression and a reduction in amplitude. In this study, we expand these early observations by exploring the development of non-visual light sensitivity and clock function between surface and cave populations. When does the circadian pacemaker begin to oscillate during development, and are there differences between the various strains? Is the difference in acute light sensitivity, seen in adults, apparent from the earliest stages of development? Our results show that both cave and surface populations must experience daily light exposure to establish a larval gene expression rhythm. These oscillations begin early, around the third day of development in all strains, but gene expression rhythms show a significantly higher amplitude in surface fish larvae. In addition, the light induction of clock genes is developmentally delayed in cave populations. Zebrafish embryonic light sensitivity has been shown to be critical not only for clock entrainment, but also for transcriptional activation of DNA repair processes. Similar downstream transcriptional responses to light also occur in Astyanax. Interestingly, the establishment of the adult timing profile of clock gene expression takes several days to become apparent. This fact may provide mechanistic insight into the key differences between the cave and surface fish clock mechanisms.
大多数动植物生活在地球上,会经历有规律的昼夜交替。因此,它们进化出了内源性生物钟来有节奏地调节自身生理机能,以及非视觉光检测机制,以便根据环境的昼夜循环来设定生物钟。就鱼类而言,昼夜节律起搏器不仅存在于大多数组织和细胞中,而且这些组织本身对光直接敏感,表达多种视蛋白光色素。这种广泛的非视觉光敏感性不仅用于设定生物钟,还会影响广泛的基本细胞生物学过程,比如DNA修复调控。在这种背景下,墨西哥丽脂鲤是一个非常有趣的模型系统,可用于探索非视觉光检测和生物钟功能。此前的研究表明,表层鱼类拥有上述同样可直接受光调节的生物钟。在实验室环境下,墨西哥丽脂鲤的洞穴种群也是如此,不过在墨西哥的自然黑暗条件下未观察到日常节律。然而,洞穴种群的光反应有明显改变,生物钟也发生了变化,基因表达峰值的相位不同,振幅减小。在本研究中,我们通过探究表层和洞穴种群之间非视觉光敏感性和生物钟功能的发育情况,扩展了这些早期观察结果。生物钟起搏器在发育过程中何时开始振荡,不同品系之间是否存在差异?在成鱼中观察到的急性光敏感性差异,在发育的最早阶段是否明显?我们的结果表明,洞穴种群和表层种群都必须经历日常光照才能建立幼虫基因表达节律。这些振荡在所有品系发育的第三天左右就开始了,但基因表达节律在表层鱼类幼虫中的振幅明显更高。此外,洞穴种群中生物钟基因的光诱导在发育上有所延迟。斑马鱼胚胎的光敏感性已被证明不仅对生物钟的调节至关重要,而且对DNA修复过程的转录激活也很关键。墨西哥丽脂鲤对光也有类似的下游转录反应。有趣的是,生物钟基因表达的成年时间模式要过几天才会明显显现。这一事实可能为深入了解洞穴鱼和表层鱼生物钟机制的关键差异提供机制上的见解。