Fresh insights into the light-induced pineal gland circadian rhythm transmission mechanism derived from mRNA and miRNA profiling

Yunlei Li , Yanyan Sun , Jingwei Yuan , Xiangchen Li , Lei Shi , Adamu Mani Isa , Yuanmei Wang , Pingzhuang Ge , Yunhe Zong , Panlin Wang , Jilan Chen

Animal Research and One Health ›› 2026, Vol. 4 ›› Issue (1) : 36 -54.

PDF
Animal Research and One Health ›› 2026, Vol. 4 ›› Issue (1) :36 -54. DOI: 10.1002/aro2.95
ARTICLE
Fresh insights into the light-induced pineal gland circadian rhythm transmission mechanism derived from mRNA and miRNA profiling
Author information +
History +
PDF

Abstract

The circadian clock significantly impacts animal health and productivity, with light playing a crucial role in regulating circadian rhythms. However, the mechanisms behind light-induced circadian transmission remain unclear, particularly in light-sensitive avian species. The pineal gland is a key component acting as the photosensitive master oscillator in the avian clock system. Using transcriptome sequencing and small RNA sequencing technologies, we identified circadian genes and miRNAs in the chick pineal gland under light–dark and sudden constant-light conditions. We observed rhythmic oscillations in up to 1299 genes during the light–dark cycle, with 400 genes maintaining rhythms under constant light. Our findings highlight the light-sensitive temporal organization in birds as the phase distribution of circadian genes in the pineal gland correlates with light exposure changes. A novel regulatory mechanism involving light, cyclic adenosine monophosphate, cyclic guanosine monophosphate, light-sensitive miRNAs, such as gga-miR-34b-5p, and light-sensitive circadian genes, such as CRY2, was discovered to participate in the light input system of the chick pineal clock, through which light regulates the oscillators and outputs of the circadian clock system. Additionally, transcriptomic analysis, liquid chromatography–mass spectrometry, and Oil Red O staining revealed cyclic changes in lipid synthesis and metabolism throughout the circadian day, which may be a key mechanism through which the circadian clock influences pineal physiology. Our results enhance the understanding of light-induced circadian transmission mechanisms and identify potential targets for optimizing the circadian clock through light.

Keywords

bird / circadian clock / light transmission / lipid metabolism / pineal gland

Cite this article

Download citation ▾
Yunlei Li, Yanyan Sun, Jingwei Yuan, Xiangchen Li, Lei Shi, Adamu Mani Isa, Yuanmei Wang, Pingzhuang Ge, Yunhe Zong, Panlin Wang, Jilan Chen. Fresh insights into the light-induced pineal gland circadian rhythm transmission mechanism derived from mRNA and miRNA profiling. Animal Research and One Health, 2026, 4(1): 36-54 DOI:10.1002/aro2.95

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Takahashi, J. S. (2017). Transcriptional architecture of the mammalian circadian clock. Nature Reviews Genetics, 18(3), 164-179. https://doi.org/10.1038/nrg.2016.150

[2]

Fishbein, A. B., Knutson, K. L., & Zee, P. C. (2021). Circadian disruption and human health. Journal of Clinical Investigation, 131(19), e148286. https://doi.org/10.1172/jci148286

[3]

Hsieh, P. N., Zhang, L., & Jain, M. K. (2017). Coordination of cardiac rhythmic output and circadian metabolic regulation in the heart. Cellular and Molecular Life Sciences, 75(3), 403-416. https://doi.org/10.1007/s00018-017-2606-x

[4]

Bailey, M. J., Beremand, P. D., Hammer, R., Bell-Pedersen, D., Thomas, T. L., & Cassone, V. M. (2003). Transcriptional profiling of the chick pineal gland, a photoreceptive circadian oscillator and pacemaker. Molecular Endocrinology, 17(10), 2084-2095. https://doi.org/10.1210/me.2003-0121

[5]

Karaganis, S. P., Kumar, V., Beremand, P. D., Bailey, M. J., Thomas, T. L., & Cassone, V. M. (2008). Circadian genomics of the chick pineal gland in vitro. BMC Genomics, 9(1), 206. https://doi.org/10.1186/1471-2164-9-206

[6]

Latimer, M. N., Williams, L. J., Shanmugan, G., Carpenter, B. J., Lazar, M. A., Dierickx, P., & Young, M. E. (2023). Cardiomyocyte-specific disruption of the circadian BMAL1-REV-ERBα/β regulatory network impacts distinct miRNA species in the murine heart. Communications Biology, 6(1), 1149. https://doi.org/10.1038/s42003-023-05537-z

[7]

Xia, X., Fu, X., Du, J., Wu, B., Zhao, X., Zhu, J., & Zhao, Z. (2020). Regulation of circadian rhythm and sleep by miR-375-timeless interaction in Drosophila. The FASEB Journal, 34(12), 16536-16551. https://doi.org/10.1096/fj.202001107R

[8]

Du, X., Cui, Z., Ning, Z., Deng, X., Amevor, F. K., Shu, G., Wang, X., Zhang, Z., Tian, Y., Zhu, Q., Wang, Y., Li, D., Zhang, Y., & Zhao, X. (2022). Circadian miR-218-5p targets gene CA2 to regulate uterine carbonic anhydrase activity during egg shell calcification. Poultry Science, 101(11), 102158. https://doi.org/10.1016/j.psj.2022.102158

[9]

Shende, V. R., Neuendorff, N., & Earnest, D. J. (2013). Role of miR-142-3p in the post-transcriptional regulation of the clock gene Bmal1 in the mouse SCN. PLoS One, 8(6), e65300. https://doi.org/10.1371/journal.pone.0065300

[10]

Tan, X., Zhang, P., Zhou, L., Yin, B., Pan, H., & Peng, X. (2012). Clock-controlled mir-142-3p can target its activator, Bmal1. BMC Molecular Biology, 13(1), 27. https://doi.org/10.1186/1471-2199-13-27

[11]

Nagel, R., Clijsters, L., & Agami, R. (2009). The miRNA-192/194 cluster regulates the Period gene family and the circadian clock. FEBS Journal, 276(19), 5447-5455. https://doi.org/10.1111/j.1742-4658.2009.07229.x

[12]

Gao, Q., Zhou, L., Yang, S. Y., & Cao, J. M. (2016). A novel role of microRNA 17-5p in the modulation of circadian rhythm. Scientific Reports, 6(1), 30070. https://doi.org/10.1038/srep30070

[13]

Zhou, L., Miller, C., Miraglia, L. J., Romero, A., Mure, L. S., Panda, S., & Kay, S. A. (2021). A genome-wide microRNA screen identifies the microRNA-183/96/182 cluster as a modulator of circadian rhythms. Proceedings of the National Academy of Sciences of the United States of America, 118(1), e2020454118. https://doi.org/10.1073/pnas.2020454118

[14]

Menaker, M., & Underwood, H. (1976). Extraretinal photoreception in birds. Photophysiology, 23(4), 299-306. https://doi.org/10.1111/j.1751-1097.1976.tb07251.x

[15]

Erofeeva, N., Meshalkina, D., & Firsov, M. (2023). Multiple roles of cAMP in vertebrate retina. Cells, 12(8), 1157. https://doi.org/10.3390/cells12081157

[16]

Astakhova, L. A., Samoiliuk, E. V., Govardovskii, V. I., & Firsov, M. L. (2012). cAMP controls rod photoreceptor sensitivity via multiple targets in the phototransduction cascade. Journal of General Physiology, 140(4), 421-433. https://doi.org/10.1085/jgp.201210811

[17]

Wainwright, S. D. (1980). Diurnal cycles in serotonin acetyltransferase activity and cyclic GMP content of cultured chick pineal glands. Nature, 285(5765), 478-480. https://doi.org/10.1038/285478a0

[18]

Ivanova, T. N., & Iuvone, P. M. (2003). Circadian rhythm and photic control of cAMP level in chick retinal cell cultures: A mechanism for coupling the circadian oscillator to the melatonin-synthesizing enzyme, arylalkylamine N-acetyltransferase, in photoreceptor cells. Brain Research, 991(1–2), 96-103. https://doi.org/10.1016/j.brainres.2003.08.003

[19]

Mure, L. S., Le, H. D., Benegiamo, G., Chang, M. W., Rios, L., Jillani, N., Ngotho, M., Kariuki, T., Dkhissi-Benyahya, O., Cooper, H. M., & Panda, S. (2018). Diurnal transcriptome atlas of a primate across major neural and peripheral tissues. Science, 359(6381), eaao0318. https://doi.org/10.1126/science.aao0318

[20]

Li, H., Zhang, S., Zhang, W., Chen, S., Rabearivony, A., Shi, Y., Liu, J., Corton, C. J., & Liu, C. (2020). Endogenous circadian time genes expressions in the liver of mice under constant darkness. BMC Genomics, 21(1), 224. https://doi.org/10.1186/s12864-020-6639-4

[21]

Wu, G., Anafi, R. C., Hughes, M. E., Kornacker, K., & Hogenesch, J. B. (2016). MetaCycle: An integrated R package to evaluate periodicity in large scale data. Bioinformatics, 32(21), 3351-3353. https://doi.org/10.1093/bioinformatics/btw405

[22]

Coesel, S. N., Durham, B. P., Groussman, R. D., Hu, S. K., Caron, D. A., Morales, R. L., Ribalet, F., & Armbrust, E. V. (2021). Diel transcriptional oscillations of light-sensitive regulatory elements in open-ocean eukaryotic plankton communities. Proceedings of the National Academy of Sciences of the United States of America, 118(6). https://doi.org/10.1073/pnas.2011038118

[23]

Bailey, M. J., Coon, S. L., Carter, D. A., Humphries, A., Kim, J. S., Shi, Q., Gaildrat, P., Morin, F., Ganguly, S., Hogenesch, J. B., Weller, J. L., Rath, M. F., Møller, M., Baler, R., Sugden, D., Rangel, Z. G., Munson, P. J., & Klein, D. C. (2009). Night/day changes in pineal expression of >600 genes: Central role of adrenergic/cAMP signaling. Journal of Biological Chemistry, 284(12), 7606-7622. https://doi.org/10.1074/jbc.M808394200

[24]

Coon, S. L., Munson, P. J., Cherukuri, P. F., Sugden, D., Rath, M. F., Møller, M., Clokie, S. J., Fu, C., Olanich, M. E., Rangel, Z., Werner, T., Mullikin, J. C., Klein, D. C., Benjamin, B., Blakesley, R., Bouffard, G., Brooks, S., Chu, G., Coleman, H., & Young, A. (2012). Circadian changes in long noncoding RNAs in the pineal gland. Proceedings of the National Academy of Sciences of the United States of America, 109(33), 13319-13324. https://doi.org/10.1073/pnas.1207748109

[25]

Kommedal, S., Csernus, V., & Nagy, A. D. (2013). The embryonic pineal gland of the chicken as a model for experimental jet lag. General and Comparative Endocrinology, 188, 226-231. https://doi.org/10.1016/j.ygcen.2013.04.006

[26]

Wang, P., Sun, Y., Li, Y., Fan, J., Zong, Y., Isa, A. M., Shi, L., Wang, Y., Ni, A., Ge, P., Jiang, L., Bian, S., Ma, H., Yuan, Z., Liu, X., & Chen, J. (2021). Monochromatic green light stimulation during incubation shortened the hatching time via pineal function in White Leghorn eggs. Journal of Animal Science and Biotechnology, 12(1), 17. https://doi.org/10.1186/s40104-020-00539-x

[27]

Wang, G. Z., Hickey, S. L., Shi, L., Huang, H. C., Nakashe, P., Koike, N., Tu, B. P., Takahashi, J. S., & Konopka, G. (2015). Cycling transcriptional networks optimize energy utilization on a genome scale. Cell Reports, 13(9), 1868-1880. https://doi.org/10.1016/j.celrep.2015.10.043

[28]

Zhang, R., Lahens, N. F., Ballance, H. I., Hughes, M. E., & Hogenesch, J. B. (2014). A circadian gene expression atlas in mammals: Implications for biology and medicine. Proceedings of the National Academy of Sciences of the United States of America, 111(45), 16219-16224. https://doi.org/10.1073/pnas.1408886111

[29]

Haque, R., Ali, F. G., Biscoglia, R., Abey, J., Weller, J., Klein, D., & Iuvone, P. M. (2010). CLOCK and NPAS2 have overlapping roles in the circadian oscillation of arylalkylamine N-acetyltransferase mRNA in chicken cone photoreceptors. Journal of Neurochemistry, 113(5), 1296-1306. https://doi.org/10.1111/j.1471-4159.2010.06698.x

[30]

Hatori, M., Gill, S., Mure, L. S., Goulding, M., O'Leary, D. D., & Panda, S. (2014). Lhx1 maintains synchrony among circadian oscillator neurons of the SCN. Elife, 3, e03357. https://doi.org/10.7554/eLife.03357

[31]

Okano, T., & Fukada, Y. (2003). Chicktacking pineal clock. Journal of Biochemistry, 134(6), 791-797. https://doi.org/10.1093/jb/mvg221

[32]

Yoshimura, T., Suzuki, Y., Makino, E., Suzuki, T., Kuroiwa, A., Matsuda, Y., Namikawa, T., & Ebihara, S. (2000). Molecular analysis of avian circadian clock genes. Brain Research. Molecular Brain Research, 78(1–2), 207-215. https://doi.org/10.1016/s0169-328x(00)00091-7

[33]

Yasuo, S., Yoshimura, T., Bartell, P. A., Iigo, M., Makino, E., Okabayashi, N., & Ebihara, S. (2002). Effect of melatonin administration on qPer2, qPer3, and qClock gene expression in the suprachiasmatic nucleus of Japanese quail. European Journal of Neuroscience, 16(8), 1541-1546. https://doi.org/10.1046/j.1460-9568.2002.02222.x

[34]

Paul, M., Golla, K., & Kim, H. (2022). Gelsolin modulates platelet dense granule secretion and hemostasis via the actin cytoskeleton. Thrombosis & Haemostasis, 123(2), 219-230. https://doi.org/10.1055/s-0042-1758800

[35]

LeGates, T. A., Fernandez, D. C., & Hattar, S. (2014). Light as a central modulator of circadian rhythms, sleep and affect. Nature Reviews Neuroscience, 15(7), 443-454. https://doi.org/10.1038/nrn3743

[36]

Xue, J., Han, Y., Zeng, W., & Jiang, Y. (2022). Structural mechanisms of assembly, permeation, gating, and pharmacology of native human rod CNG channel. Neuron, 110(1), 86-95. https://doi.org/10.1016/j.neuron.2021.10.006

[37]

Dryer, S. E., & Henderson, D. (1991). A cyclic GMP-activated channel in dissociated cells of the chick pineal gland. Nature, 353(6346), 756-758. https://doi.org/10.1038/353756a0

[38]

D'Souza, T., & Dryer, S. E. (1996). A cationic channel regulated by a vertebrate intrinsic circadian oscillator. Nature, 382(6587), 165-167. https://doi.org/10.1038/382165a0

[39]

Takahashi, J. S., & Zatz, M. (1982). Regulation of circadian rhythmicity. Science, 217(4565), 1104-1111. https://doi.org/10.1126/science.6287576

[40]

Zatz, M., & Mullen, D. A. (1988). Photoendocrine transduction in cultured chick pineal cells. II. Effects of forskolin, 8-bromocyclic AMP, and 8-bromocyclic GMP on the melatonin rhythm. Brain Research, 453(1–2), 51-62. https://doi.org/10.1016/0006-8993(88)90142-4

[41]

Zatz, M., & Mullen, D. A. (1988). Two mechanisms of photoendocrine transduction in cultured chick pineal cells: Pertussis toxin blocks the acute but not the phase-shifting effects of light on the melatonin rhythm. Brain Research, 453(1–2), 63-71. https://doi.org/10.1016/0006-8993(88)90143-6

[42]

Cheng, H. Y., Papp, J. W., Varlamova, O., Dziema, H., Russell, B., Curfman, J. P., Nakazawa, T., Shimizu, K., Okamura, H., Impey, S., & Obrietan, K. (2007). MicroRNA modulation of circadian-clock period and entrainment. Neuron, 54(5), 813-829. https://doi.org/10.1016/j.neuron.2007.05.017

[43]

Sangma, J. T., & Trivedi, A. K. (2023). Light at night: Effect on the daily clock, learning, memory, cognition, and expression of transcripts in different brain regions of rat. Photochemical and Photobiological Sciences, 22(10), 2297-2314. https://doi.org/10.1007/s43630-023-00451-z

[44]

Devasani, K., & Yao, Y. (2022). Expression and functions of adenylyl cyclases in the CNS. Fluids and Barriers of the CNS, 19(1), 23. https://doi.org/10.1186/s12987-022-00322-2

[45]

Zatz, M., Gastel, J. A., Heath, J. R., III, & Klein, D. C. (2000). Chick pineal melatonin synthesis: Light and cyclic AMP control abundance of serotonin N-acetyltransferase protein. Journal of Neurochemistry, 74(6), 2315-2321. https://doi.org/10.1046/j.1471-4159.2000.0742315.x

[46]

Reinke, H., & Asher, G. (2019). Crosstalk between metabolism and circadian clocks. Nature Reviews Molecular Cell Biology, 20(4), 227-241. https://doi.org/10.1038/s41580-018-0096-9

[47]

Solocinski, K., & Gumz, M. L. (2015). The circadian clock in the regulation of renal rhythms. Journal of Biological Rhythms, 30(6), 470-486. https://doi.org/10.1177/0748730415610879

[48]

Petrenko, V., Saini, C., Giovannoni, L., Gobet, C., Sage, D., Unser, M., Heddad Masson, M., Gu, G., Bosco, D., Gachon, F., Philippe, J., & Dibner, C. (2017). Pancreatic α- and β-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression. Genes & Development, 31(4), 383-398. https://doi.org/10.1101/gad.290379.116

[49]

Klein, D. C., Coon, S. L., Roseboom, P. H., Weller, J. L., Bernard, M., Gastel, J. A., Zatz, M., Iuvone, P. M., Rodriguez, I. R., Bégay, V., Falcón, J., Cahill, G. M., Cassone, V. M., & Baler, R. (1997). The melatonin rhythm-generating enzyme: Molecular regulation of serotonin N-acetyltransferase in the pineal gland. Recent Progress in Hormone Research, 52, 307-357.

[50]

Bernard, M., Iuvone, P. M., Cassone, V. M., Roseboom, P. H., Coon, S. L., & Klein, D. C. (1997). Avian melatonin synthesis: Photic and circadian regulation of serotonin N-acetyltransferase mRNA in the chicken pineal gland and retina. Journal of Neurochemistry, 68(1), 213-224. https://doi.org/10.1046/j.1471-4159.1997.68010213.x

[51]

Gorman, M. R. (2020). Temporal organization of pineal melatonin signaling in mammals. Molecular and Cellular Endocrinology, 503, 110687. https://doi.org/10.1016/j.mce.2019.110687

[52]

Johnson, A. L., Foss, D. C., & Carew, L. B. (1980). Pineal gland lipid characterization in the seven-week-old cockerel (Gallus domesticus). Poultry Science, 59(12), 2771-2775. https://doi.org/10.3382/ps.0592771

[53]

Wainwright, S. D., & Wainwright, L. K. (1985). Effects of some fatty acids on the serotonin N-acetyltransferase activity in cultured chick pineal glands. Journal of Pineal Research, 2(3), 287-299. https://doi.org/10.1111/j.1600-079x.1985.tb00646.x

[54]

Neves, A. R., Albuquerque, T., Quintela, T., & Costa, D. (2022). Circadian rhythm and disease: Relationship, new insights, and future perspectives. Journal of Cellular Physiology, 237(8), 3239-3256. https://doi.org/10.1002/jcp.30815

[55]

Love, M. I., Huber, W., & Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biology, 15(12), 550. https://doi.org/10.1186/s13059-014-0550-8

[56]

Friedländer, M. R., Chen, W., Adamidi, C., Maaskola, J., Einspanier, R., Knespel, S., & Rajewsky, N. (2008). Discovering microRNAs from deep sequencing data using miRDeep. Nature Biotechnology, 26(4), 407-415. https://doi.org/10.1038/nbt1394

[57]

Mele, M., Ferreira, P. G., Reverter, F., DeLuca, D. S., Monlong, J., Sammeth, M., Young, T. R., Goldmann, J. M., Pervouchine, D. D., Sullivan, T. J., Johnson, R., Segre, A. V., Djebali, S., Niarchou, A., Consortium, G. T., Wright, F. A., Lappalainen, T., Calvo, M., Getz, G., … Guigo, R. (2015). Human genomics. The human transcriptome across tissues and individuals. Science, 348(6235), 660-665. https://doi.org/10.1126/science.aaa0355

[58]

Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods, 25(4), 402-408. https://doi.org/10.1006/meth.2001.1262

[59]

Navigatore-Fonzo, L. S., Delgado, S. M., Gimenez, M. S., & Anzulovich, A. C. (2014). Daily rhythms of catalase and glutathione peroxidase expression and activity are endogenously driven in the hippocampus and are modified by a vitamin A-free diet. Nutritional Neuroscience, 17(1), 21-30. https://doi.org/10.1179/1476830513y.0000000062

[60]

Singh, D., Rani, S., & Kumar, V. (2013). Daily expression of six clock genes in central and peripheral tissues of a night-migratory songbird: Evidence for tissue-specific circadian timing. Chronobiology International, 30(10), 1208-1217. https://doi.org/10.3109/07420528.2013.810632

RIGHTS & PERMISSIONS

2024 The Author(s). Animal Research and One Health published by John Wiley & Sons Australia, Ltd on behalf of Institute of Animal Science, Chinese Academy of Agricultural Sciences.

PDF

19

Accesses

0

Citation

Detail

Sections
Recommended

/