Université de Lyon, Université Claude Bernard Lyon 1, Ecole Normale Supérieure de Lyon; CNRS UMR 5242, Institut de Génomique Fonctionnelle de Lyon, 46 allée d'Italie, 69364, Lyon, France.
Université Côte d'Azur, CNRS UMR7277, INSERM U1091, Institut de Biologie Valrose, Bâtiment de Sciences Naturelles, 28 Avenue Valrose, 06108, Nice Cedex 2, France.
Cell Mol Life Sci. 2018 Nov;75(21):3991-4005. doi: 10.1007/s00018-018-2845-5. Epub 2018 May 26.
Most living organisms show circadian rhythms in physiology and behavior. These oscillations are generated by endogenous circadian clocks, present in virtually all cells where they control key biological processes. To study peripheral clocks in vivo, we developed an original model, the Rev-Luc mouse to follow noninvasively and longitudinally Rev-Luc oscillations in peripheral clocks using in vivo bioluminescence imaging. We found in vitro and in vivo a robust diurnal rhythm of Rev-Luc, mainly in liver, intestine, kidney and adipose tissues. We further confirmed in vivo that Rev-Luc peripheral tissues are food-entrainable oscillators, not affected by age or sex. These data strongly support the relevance of the Rev-Luc model for circadian studies, especially to investigate in vivo the establishment and the entrainment of the rhythm throughout ontogenesis. We then showed that Rev-Luc expression develops dynamically and gradually, both in amplitude and in phase, during fetal and postnatal development. We also demonstrate for the first time that the immature peripheral circadian system of offspring in utero is mainly entrained by maternal cues from feeding regimen. The prenatal entrainment will also differentially determine the Rev-Luc expression in pups before weaning underlining the importance of the maternal chrononutrition on the circadian system entrainment of the offspring.
大多数生物的生理和行为都表现出昼夜节律。这些振荡是由内源性生物钟产生的,几乎存在于所有控制关键生物过程的细胞中。为了在体内研究外周生物钟,我们开发了一种原始模型,即 Rev-Luc 小鼠,用于使用活体生物发光成像非侵入性和纵向地跟踪外周生物钟的 Rev-Luc 振荡。我们发现 Rev-Luc 在体外和体内都有很强的昼夜节律,主要在肝脏、肠道、肾脏和脂肪组织中。我们进一步在体内证实,Rev-Luc 外周组织是受食物调节的振荡器,不受年龄或性别的影响。这些数据强烈支持 Rev-Luc 模型在昼夜节律研究中的相关性,特别是用于研究整个胚胎发生过程中体内节律的建立和同步。然后我们表明,Rev-Luc 的表达在胎儿和产后发育过程中在幅度和相位上都动态地逐渐发展。我们还首次证明,宫内胎儿未成熟的外周昼夜节律系统主要受母体喂养方案的线索调节。产前同步也会在断奶前不同程度地决定幼崽的 Rev-Luc 表达,这突出了母体 chrononutrition 对后代昼夜节律系统同步的重要性。