Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture

Sabado, Virginie; Vienne, Ludovic; Nagoshi, Emi

doi:10.3389/fncel.2017.00317

Cited by 8 publications

(4 citation statements)

References 57 publications

(89 reference statements)

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“…It is also likely that circadian signaling occurs between ISCs and EBs in this tissue, because disruption of the N pathway in ISC/EBs using the esg driver results in loss of rhythmicity in ISCs, which do not require N signaling. This ability to synchronize circadian timing between different intestinal cells bears some similarity to neuronal clocks of the brain, whereby clock-harboring cells communicate with one another to achieve a unified circadian output ( Liu et al., 2007 , Sabado et al., 2017 ). Although intestinal cells are clearly not so interdependent as neurons, a large repertoire of signaling processes are known to occur between intestinal cells ( Biteau et al., 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Intestinal Stem Cells Exhibit Conditional Circadian Clock Function

et al. 2018

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SummaryThe circadian clock is a molecular pacemaker that produces 24-hr physiological cycles known as circadian rhythms. How the clock regulates stem cells is an emerging area of research with many outstanding questions. We tested clock function in vivo at the single cell resolution in the Drosophila intestine, a tissue that is exquisitely sensitive to environmental cues and has circadian rhythms in regeneration. Our results indicate that circadian clocks function in intestinal stem cells and enterocytes but are downregulated during enteroendocrine cell differentiation. Drosophila intestinal cells are principally synchronized by the photoperiod, but intestinal stem cell clocks are highly responsive to signaling pathways that comprise their niche, and we find that the Wnt and Hippo signaling pathways positively regulate stem cell circadian clock function. These data reveal that intestinal stem cell circadian rhythms are regulated by cellular signaling and provide insight as to how clocks may be altered during physiological changes such as regeneration and aging.

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Section: Discussionmentioning

confidence: 99%

Intestinal Stem Cells Exhibit Conditional Circadian Clock Function

et al. 2018

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“…Welsh and coworkers first reported that neurons within the suprachiasmatic nucleus (SCN; the master pacemaker in the hypothalamus of mammals) are surprisingly heterogeneous in their intrinsic periods of circadian firing pattern [4]. Subsequent studies revealed that such period heterogeneity is not restricted to the SCN but is also observed in mammalian peripheral clock cells [5,6] as well as in Drosophila clock cells [7] and plants [8,9]. The ubiquity of this phenomenon suggests that heterogeneity may be functionally relevant for circadian clocks [10][11][12][13][14][15][16][17][18], thus likely being a substrate for natural selection.…”

Section: Introductionmentioning

confidence: 99%

Heritable gene expression variability and stochasticity govern clonal heterogeneity in circadian period

2020

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A ubiquitous feature of the circadian clock across life forms is its organization as a network of cellular oscillators, with individual cellular oscillators within the network often exhibiting considerable heterogeneity in their intrinsic periods. The interaction of coupling and heterogeneity in circadian clock networks is hypothesized to influence clock's entrainability, but our knowledge of mechanisms governing period heterogeneity within circadian clock networks remains largely elusive. In this study, we aimed to explore the principles that underlie intercellular period variation in circadian clock networks (clonal period heterogeneity). To this end, we employed a laboratory selection approach and derived a panel of 25 clonal cell populations exhibiting circadian periods ranging from 22 to 28 h. We report that a single parent clone can produce progeny clones with a wide distribution of circadian periods, and this heterogeneity, in addition to being stochastically driven, has a heritable component. By quantifying the expression of 20 circadian clock and clock-associated genes across our clone panel, we found that inheritance of expression patterns in at least three clock genes might govern clonal period heterogeneity in circadian clock networks. Furthermore, we provide evidence suggesting that heritable epigenetic variation in gene expression regulation might underlie period heterogeneity.

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“…Welsh and co-workers first reported that neurons within the suprachiasmatic nucleus (SCN; the master pacemaker in the hypothalamus of mammals) are surprisingly heterogeneous in their intrinsic periods of circadian firing pattern (Welsh et al, 1995). Subsequent studies revealed that such period-heterogeneity is not restricted to the SCN alone, but is also characteristic of mammalian peripheral clock cells (Nagoshi et al, 2004;Leise et al, 2012) as well as of clock cells in Drosophila (Sabado et al, 2017) and plants (Yakir et al, 2011;Muranaka and Oyama, 2016). The ubiquity of this network feature suggests that heterogeneity may be functionally relevant for circadian clocks (Jagota et al, 2000;Schaap et al, 2003;Gonze et al, 2005;Bernar0d et al, 2007;Inagaki et al, 2007;VanderLeest et al, 2007;Gu et al, 2016Gu et al, , 2019, thus likely being a substrate for natural selection.…”

Section: Introductionmentioning

confidence: 99%

Heritable gene expression variability governs clonal heterogeneity in circadian period

Nikhil

Korge

Kramer

2019

Preprint

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11A ubiquitous feature of circadian clocks across life forms is its organization as a network of 12 coupled cellular oscillators. Individual cellular oscillators of the network often exhibit a 13 considerable degree of heterogeneity in their intrinsic periods. While the interaction of coupling 14 and heterogeneity in circadian clock networks is hypothesized to influence clock's entrainability, 15 our knowledge of mechanisms governing network heterogeneity remains elusive. In this study, 16 we aimed to explore the principles that underlie inter-cellular period variation in circadian clock 17 networks (clonal period-heterogeneity). To this end, we employed a laboratory selection 18 approach and derived a panel of 25 clonal cell populations exhibiting circadian periods ranging 19 from 22 h to 28 h. We report that while a single parent clone can produce progeny clones with a 20 wide distribution of circadian periods, heterogeneity is not entirely stochastically driven but has 21 a strong heritable component. By quantifying the expression of 20 circadian clock and clock-22 associated genes across our panel, we found that inheritance of different expression patterns in 23 at least three clock genes might govern clonal period-heterogeneity in circadian clock networks. 24 Furthermore, we provide preliminary evidence suggesting that epigenetic variation might 25 underlie such gene expression variation. 26 27 Evans et al., 2018). In this study, we aimed to explore the possible mechanisms underlying clonal-55 heterogeneity of circadian period in human circadian oscillator cells. 56 We hypothesised that clonal period-heterogeneity in mammalian cells is due to a) stochastic 57 variation (Geva-Zatorsky et al., 2006; Chang et al., 2008; Brock, Chang and Huang, 2009; Frank 58 and Rosner, 2012) and/or b) heritable variation (Dubnau and Losick, 2006; Gordon et al., 2009, 59 2013). Since the term 'stochastic' is used in the context of both non-heritable (external noise and 60 gene expression noise) as well as heritable gene expression variation (epigenetic stochasticity), 61 for the rest of this manuscript we define 'stochasticity' as any non-heritable variation (both 62 internal and external). To test the two hypothesis outlined above, we employed a laboratory 63 selection approach and derived a panel of 25 clonal cell lines (from a common ancestral/founding 64 culture) exhibiting a range of periods between 22h and 28h. We observed that the period-65 heterogeneity among progeny clones stemming from a single parent cell is not entirely stochastic 66 but has a substantial heritable component. We then measured expression of 20 clock and clock-67 associated genes in our panel and observed that variation in gene expression levels of at least 68 three clock genes (transcription factors) might underlie clonal period-heterogeneity. 69 Furthermore, we provide preliminary evidence that epigenetic variation might govern the 70 observed clonal-variation in gene expression. 71 72 73 74 75 157 period while D...

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Evaluating the Autonomy of the Drosophila Circadian Clock in Dissociated Neuronal Culture

Cited by 8 publications

References 57 publications

Intestinal Stem Cells Exhibit Conditional Circadian Clock Function

Intestinal Stem Cells Exhibit Conditional Circadian Clock Function

Heritable gene expression variability and stochasticity govern clonal heterogeneity in circadian period

Heritable gene expression variability governs clonal heterogeneity in circadian period

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