Ontogeny of Circadian Rhythms and Synchrony in the Suprachiasmatic Nucleus

Carmona‐Alcocer, Vania; Abel, John H.; Sun, Tao; Petzold, Linda R.; Doyle, Francis J.; Simms, Carrie L.; Herzog, Erik D.

doi:10.1523/jneurosci.2006-17.2017

Cited by 80 publications

(92 citation statements)

References 66 publications

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“…Accordingly, the VIP‐like immunoreactivity has also been detected in cells and fibers of the rat SCN prior to birth, although the neurons appear to be morphologically immature, and their distribution differs from that seen in the adult SCN (Laemle, ). Surprisingly, in a recent study, an absence of the VIP and its receptors (VIPAC2R) in the fetal mouse SCN was reported (Carmona‐Alcocer et al., ).…”

Section: Morphological Development Of the Scnmentioning

confidence: 98%

Mystery of rhythmic signal emergence within the suprachiasmatic nuclei

Sumová

Čečmanová

2018

Eur J of Neuroscience

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The circadian system provides organisms with a temporal organization that optimizes their adaptation to environmental fluctuations on a 24-hr basis. In mammals, the circadian clock in the suprachiasmatic nuclei (SCN) develops during the perinatal period. The rhythmicity first appears at the level of individual SCN neurons during the fetal stage, and this step is often misinterpreted as the time of complete SCN clock development. However, the process is only finalized when the SCN begin to play a role of the central clock in the body, that is, when they are able to generate robust rhythmicity at the cell population level, entrain the rhythmic signal with external light-dark cycles and convey this signal to the rest of the body. The development is gradual and correlates with morphological maturation of the SCN structural complexity, which is based on intercellular network formation. The aim of this review is to summarize events related to the first emergence of circadian oscillations in the fetal SCN clock. Although a large amount of data on ontogenesis of the circadian system have been accumulated, how exactly the immature SCN converts into a functional central clock has still remained rather elusive. In this review, the hypothesis of how the SCN attains its rhythmicity at the tissue level is discussed in context with the recent advances in the field. For an extensive summary of the complete ontogenetic development of the circadian system, the readers are referred to other previously published reviews.

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Section: Morphological Development Of the Scnmentioning

confidence: 98%

Mystery of rhythmic signal emergence within the suprachiasmatic nuclei

Sumová

Čečmanová

2018

Eur J of Neuroscience

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“…Circadian oscillations of the core clock genes are also evident in the late stage of gestation. Recent studies have shown circadian oscillations of Per2 Luc reporter expression in ex vivo cultures of fetal mouse SCN slices isolated at E14.5 or later, corresponding to the crucial period for SCN development and neurogenesis 29–31 . Peripheral circadian oscillators also develop during ontogeny 32 .…”

Section: Emergence Of the Circadian Clock During Ontogenesismentioning

confidence: 99%

“…These reports strongly suggest that fetal peripheral tissues and cells spontaneously develop self‐sustaining circadian gene expression rhythms without maternal signals. In contrast to peripheral tissues, the SCN explanted at E13.5 is reported to be arrhythmic and to remain arrhythmic during the course of ex vivo culture, suggesting that signals from the environment might be required for the development of the master circadian regulator in the SCN 31 …”

Section: Emergence Of the Circadian Clock During Ontogenesismentioning

confidence: 99%

Circadian clock and cancer: From a viewpoint of cellular differentiation

2020

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Abbreviations & Acronyms AML = acute myeloid leukemia ccg = clock-controlled gene DNMT1 = DNA methyltransferase 1 E19 = embryonic day 19 ES = embryonic stem iPS = induced pluripotent stem MEF = mouse embryonic fibroblast MRT = malignant rhabdoid tumor OSKM = Oct3/4, Sox2, Klf4 and c-Myc Per2 Luc = Per2::Luciferase SCN = suprachiasmatic nucleus SMG = submandibular gland TTFL = transcriptionaltranslational feedback loop UPR = unfolded protein response Correspondence: KazuhiroAbstract: The circadian clock controls and adapts diverse physiological and behavioral processes according to Earth's 24-h cycle of environmental changes. The master pacemaker of the mammalian circadian clock resides in the hypothalamic suprachiasmatic nucleus, but almost all cells throughout the body show circadian oscillations in gene expression patterns and associated functions. Recent studies have shown that the circadian clock gradually develops during embryogenesis. Embryonic stem cells and induced pluripotent stem cells do not show circadian oscillations of gene expression, but gradually develop circadian clock oscillation during differentiation; thus, the developmental program of circadian clock emergence appears closely associated with cellular differentiation. Like embryonic stem cells, certain cancer cell types also lack the circadian clock. Given this similarity between embryonic stem cells and cancer cells, interest is growing in the contributions of circadian clock dysfunction to dedifferentiation and cancer development. In this review, we summarize recent advances in our understanding of circadian clock emergence during ontogenesis, and discuss possible associations with cellular differentiation and carcinogenesis. Considering the multiple physiological functions of circadian rhythms, circadian abnormalities might contribute to a host of diseases, including cancer. Insights on circadian function could lead to the identification of biomarkers for cancer diagnosis and prognosis, as well as novel targets for treatment. Hierarchical organization of the mammalian circadian clockMost organisms have evolved an intrinsic circadian clock to adapt physiological functions to the planet's 24-h environmental cycles. In mammals, the circadian clock controls such physiological and behavioral functions as sleep-wake cycles, metabolism, hormonal secretion, body temperature, immune responses and neuronal functions. 1,2 The master pacemaker of the mammalian circadian clock resides in the SCN of the hypothalamus. A subset of SCN neurons receive a clock-resetting light signal from the retinohypothalamic tract and communicate with other SCN cells to maintain robust circadian oscillations of neuronal activity. These neuronal oscillations in turn synchronize other peripheral oscillators throughout the body through neuronal and hormonal signaling pathways. 3,4 At the cellular and molecular levels, the circadian clock is comprised of a set of core clock genes functionally organized into TTFLs that generate cell-autonomous circadian oscillations in gene ex...

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“…However, mutant mice that lack connexins, or those lacking VIP or the VIP receptor, do not show complete abolishment of coupling (Herzog et al, 2017). Similarly, a recent study of the ontogeny of SCN synchrony indicated that such synchrony appears prior to the expression of VIP (Carmona-Alcocer et al, 2018). Therefore, it is parsimonious to conclude that the DDCS network, with its high preference for ipRGC input, offers a plausible network motif within the SCN to enhance the effect of ipRGC signals, thus achieving a strong response within this nucleus to light input.…”

Section: Iprgc Axons Within Different Brain Regions Have Structurallymentioning

confidence: 99%

Synaptic Specializations of Melanopsin-Retinal Ganglion Cells in Multiple Brain Regions Revealed by Genetic Label for Light and Electron Microscopy

Kim

Rios

et al. 2019

Cell Reports

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Graphical Abstract Highlights d Membrane-tethered miniSOG for correlated light and electron microscopy in vivo d Melanopsin RGCs show brain region-specific arborization and synaptic structures d A subset of SCN neurons network through dendrodendritic chemical synapses (DDCS) d SCN neurons in DDCS network receive a higher melanopsin RGC input SUMMARYThe form and synaptic fine structure of melanopsinexpressing retinal ganglion cells, also called intrinsically photosensitive retinal ganglion cells (ipRGCs), were determined using a new membrane-targeted version of a genetic probe for correlated light and electron microscopy (CLEM). ipRGCs project to multiple brain regions, and because the method labels the entire neuron, it was possible to analyze nerve terminals in multiple retinorecipient brain regions, including the suprachiasmatic nucleus (SCN), olivary pretectal nucleus (OPN), and subregions of the lateral geniculate. Although ipRGCs provide the only direct retinal input to the OPN and SCN, ipRGC terminal arbors and boutons were found to be remarkably different in each target region. A network of dendro-dendritic chemical synapses (DDCSs) was also revealed in the SCN, with ipRGC axon terminals preferentially synapsing on the DDCS-linked cells.The methods developed to enable this analysis should propel other CLEM studies of long-distance brain circuits at high resolution. AUTHOR CONTRIBUTIONSM.H.E. played a key role in SBEM data collection for the project, and S. Panda played a key role in the biology and data analyses of this project. Quantitative Data Analyses, K

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Ontogeny of Circadian Rhythms and Synchrony in the Suprachiasmatic Nucleus

Cited by 80 publications

References 66 publications

Mystery of rhythmic signal emergence within the suprachiasmatic nuclei

Mystery of rhythmic signal emergence within the suprachiasmatic nuclei

Circadian clock and cancer: From a viewpoint of cellular differentiation

Synaptic Specializations of Melanopsin-Retinal Ganglion Cells in Multiple Brain Regions Revealed by Genetic Label for Light and Electron Microscopy

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