Clock-controlled vitamin A regulation of animal photoperiodic responsiveness

地球上的生命受到每日和季节变化的影响，这些变化与日出和日落的时间密切相关，日落是一天的长度。对于生活在温带纬度的生物来说，日长的季节性变化(也称为光周期)是发育、生理和行为的季节性反应的关键调节因素。为了适应有节奏的环境，动物、植物和微生物进化出了被称为生物钟的计时器。这些时钟调节分子通路的节律性，进而影响季节变化，但动物对日长变化如何感知并转化为季节性变化仍知之甚少。生物钟调节季节生物的一种方式是通过大脑中维生素A的节律调节。该项目将以标志性的帝王蝶为模型系统，描述维生素A在动物光周期反应中的精确作用，因为帝王蝶在迁徙行为和生殖生物学方面表现出强烈的季节性变化。由于对光周期的季节性适应在动物中普遍存在，这项工作将为不同动物群体的比较分析提供一个框架，从而对拓宽我们对季节适应的理解，使之超越迁徙物种具有深远的影响。该项目还将产生各种更广泛的影响，包括培训学生和博士后研究人员，以及在公共街道活动和当地学校开展外联活动，以提高学生和公民对君主保护的敏感度和参与度。适应变化的季节的能力在自然界中广泛存在，在许多生物体中，这种现象的主要触发因素是日长的变化(也称为光周期)。北美东部的帝王蝶Danaus plexippus是理解季节性的分子和细胞基础的强大模型。它经历了每年一次的季节性迁徙，以响应秋季光周期的减少，在此期间它进入生殖休眠，可以通过遗传操作，并且可以在实验室条件下诱导光周期反应。在这个系统中，一个功能正常的生物钟是感知和响应光周期所必需的，并参与大脑中维生素A途径的节律调节。然而，维生素A途径如何整合昼夜节律和光周期以最终调节光周期反应仍是未知的。维生素A可以产生两种不同的产物，视黄酸和维甲酸，这两种物质都会影响季节性适应。这一建议利用尖端功能基因组学和君主体内的分子工具来检验两个不相互排斥的假设：i)视网膜通过产生基于视蛋白的大脑深层光感受器来进行光周期诱导，从而调节光周期反应；以及ii)维甲酸以依赖光周期的方式重新编程基因表达，以重新连接大脑中的神经元电路，以响应季节的变化。阐明未知的光周期感光器(S)和/或昆虫光周期感知和反应的分子机制将极大地促进我们对季节性节律的分子基础的理解，这可能在动物界中被广泛保守。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Life on earth is subjected to daily and seasonal variations that are intimately linked to the timing of sunrise and sunset that sets day-length. For organisms living at temperate latitudes, seasonal changes in day-length (aka photoperiod) are key regulators of seasonal responses in development, physiology, and behavior. To adapt to a rhythmic environment, animals, plants and microbes have evolved timekeepers known as circadian clocks. These clocks regulate the rhythmicity of molecular pathways that in turn effect seasonal changes, but how changes in day-length are sensed and translated into seasonal changes remain poorly understood in animals. One way in which circadian clocks regulate seasonal biology is via the rhythmic regulation of vitamin A in the brain. This project will characterize the precise role of vitamin A in animal photoperiodic responses using the iconic monarch butterfly as a model system because monarchs exhibit strong seasonal changes in migratory behavior and reproductive biology. Because seasonal adaptations to photoperiod are ubiquitous in animals, this work will provide a framework for comparative analyses in diverse groups of animals, thus having far-reaching implications for broadening our understanding of seasonal adaptation beyond migratory species. This project will also have a variety of broader impacts, including the training of students and post-doctoral researchers, and outreach activities at public street events and local schools to sensitize and engage students and citizens alike in monarch conservation.The ability to adapt to the changing seasons is widespread in nature, and in many organisms the primary trigger for this phenomenon is changes in daylength (aka photoperiod). The Eastern North American monarch butterfly, Danaus plexippus, is a powerful model for understanding the molecular and cellular basis of seasonality. It undergoes a yearly seasonal migration in response to decreasing photoperiod in the fall during which it enters reproductive dormancy, can be genetically manipulated, and photoperiodic responses can be induced in laboratory conditions. In this system, a functional circadian clock is necessary for sensing and responding to the photoperiod, and is involved in the rhythmic regulation of the vitamin A pathway in the brain. However, how the vitamin A pathway integrates circadian and photoperiodic cycles to ultimately regulate photoperiodic responses is still unknown. Vitamin A can generate two different products, retinal and retinoic acid, which could both effect seasonal adaptations. This proposal employs cutting-edge functional genomics and molecular tools in the monarch to test two non-mutually exclusive hypotheses: i) that retinal functions in the regulation of photoperiodic responses via the production of an opsin-based deep brain photoreceptor for photoperiodic induction; and ii) that retinoic acid reprograms gene expression in a photoperiod-dependent manner to rewire the neuronal circuitry in the brain in response to changing seasons. Illuminating the yet unknown photoperiodic photoreceptor(s) and/or molecular mechanisms underlying insect photoperiodic sensing and responses will greatly advance our understanding of the molecular bases of seasonal rhythms, which are likely to be widely conserved among the animal kingdom.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.