Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University of California, 356A Med Surge II, Irvine, CA, 92697-4625, USA.
Departments of Computer Science, School of Information and Computer Sciences, University of California, Irvine, CA, 92697-4625, USA.
Mol Brain. 2024 Sep 20;17(1):67. doi: 10.1186/s13041-024-01143-0.
Primary cilia are dynamic sensory organelles that continuously undergo structural modifications in response to environmental and cellular signals, many of which exhibit rhythmic patterns. Building on our previous findings of rhythmic cilia-related gene expression in diurnal primates (baboon), this study extends the investigation to the nocturnal mouse brain to identify circadian patterns of cilia gene expression across brain regions. We used computational techniques and transcriptomic data from four publicly available databases, to examine the circadian expression of cilia-associated genes within six brain areas: brainstem, cerebellum, hippocampus, hypothalamus, striatum, and suprachiasmatic nucleus. Our analysis reveals that a substantial proportion of cilia transcripts exhibit circadian rhythmicity across the examined regions, with notable overrepresentation in the striatum, hippocampus, and cerebellum. We also demonstrate region-specific variations in the abundance and timing of circadian cilia genes' peaks, indicating an adaptation to the distinct physiological roles of each brain region. Additionally, we show that the rhythmic patterns of cilia transcripts are shifted under various physiological and pathological conditions, including modulation of the dopamine system, high-fat diet, and epileptic conditions, indicating the adaptable nature of cilia transcripts' oscillation. While limited to a few mouse brain regions, our study provides initial insights into the distinct circadian patterns of cilia transcripts and highlights the need for future research to expand the mapping across wider brain areas to fully understand the role of cilia's spatiotemporal dynamics in brain functions.
原发性纤毛是动态的感觉器官,能针对环境和细胞信号不断进行结构修饰,其中许多信号呈现节律模式。在我们之前关于昼夜节律灵长类动物(狒狒)中与纤毛相关的基因表达节律性的发现基础上,本研究将调查范围扩展到夜间活动的小鼠大脑,以确定大脑区域中纤毛基因表达的昼夜节律模式。我们使用了计算技术和来自四个公开数据库的转录组数据,来检查六个大脑区域(脑干、小脑、海马体、下丘脑、纹状体和视交叉上核)中与纤毛相关的基因的昼夜表达。我们的分析表明,相当一部分纤毛转录本在被检查的区域中表现出昼夜节律性,在纹状体、海马体和小脑中有明显的过度表达。我们还展示了昼夜节律性纤毛基因峰值在丰度和时间上的区域特异性变化,表明了每个大脑区域独特的生理功能的适应。此外,我们还表明,在各种生理和病理条件下,纤毛转录本的节律模式会发生变化,包括多巴胺系统的调节、高脂肪饮食和癫痫状态,这表明纤毛转录本的振荡具有适应性。虽然本研究仅限于少数几个小鼠大脑区域,但它为纤毛转录本的独特昼夜节律模式提供了初步见解,并强调需要进一步研究来扩大对更广泛大脑区域的映射,以全面了解纤毛时空动力学在大脑功能中的作用。