G2-phase arrest prevents bristle progenitor self-renewal and synchronizes cell divisions with cell fate differentiation

Ayeni, Joseph; Audibert, Agnès; Fichelson, Pierre; Srayko, Martin; Gho, Michel; Campbell, Shelagh D.

doi:10.1242/dev.134270

Cited by 17 publications

(17 citation statements)

References 51 publications

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“…Loss of stg , w ee1 or m yt1 expression does not affect the timing of the first division of SOPs ( Fig. 3 A-C) (which are subject to additional regulation; Ayeni et al, 2016 ). Together, these results support a model in which the opposing activities of Cdc25 and Wee1/Myt1 regulate EC division timing.…”

Section: Resultsmentioning

confidence: 97%

Coordinated control of Notch-Delta signalling and cell cycle progression drives lateral inhibition mediated tissue patterning

et al. 2016

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Coordinating cell differentiation with cell growth and division is crucial for the successful development, homeostasis and regeneration of multicellular tissues. Here, we use bristle patterning in the fly notum as a model system to explore the regulatory and functional coupling of cell cycle progression and cell fate decision-making. The pattern of bristles and intervening epithelial cells (ECs) becomes established through Notch-mediated lateral inhibition during G2 phase of the cell cycle, as neighbouring cells physically interact with each other via lateral contacts and/or basal protrusions. Since Notch signalling controls cell division timing downstream of Cdc25, ECs in lateral contact with a Delta-expressing cell experience higher levels of Notch signalling and divide first, followed by more distant neighbours, and lastly Delta-expressing cells. Conversely, mitotic entry and cell division makes ECs refractory to lateral inhibition signalling, fixing their fate. Using a combination of experiments and computational modelling, we show that this reciprocal relationship between Notch signalling and cell cycle progression acts like a developmental clock, providing a delimited window of time during which cells decide their fate, ensuring efficient and orderly bristle patterning.

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Section: Resultsmentioning

confidence: 97%

Coordinated control of Notch-Delta signalling and cell cycle progression drives lateral inhibition mediated tissue patterning

et al. 2016

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“…It is reasonable that sevoflurane may affect G1-phase in different cell types through different mechanisms. Altered G2- and M-phase duration has been reported to directly alter cell fate in neural progenitors [ 44 , 45 ], but the effect of sevoflurane on these two cell cycle phases of neural progenitors has not yet been studied in detail. In the present study, we did not find any significant differences in the expression of PH3 (Figures 6(e) and 6(f) ), an indicator of M-phase and late G2-phase [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Maternal Sevoflurane Exposure Causes Abnormal Development of Fetal Prefrontal Cortex and Induces Cognitive Dysfunction in Offspring

Song

Ling

Peng

et al. 2017

Stem Cells International

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Maternal sevoflurane exposure during pregnancy is associated with increased risk for behavioral deficits in offspring. Several studies indicated that neurogenesis abnormality may be responsible for the sevoflurane-induced neurotoxicity, but the concrete impact of sevoflurane on fetal brain development remains poorly understood. We aimed to investigate whether maternal sevoflurane exposure caused learning and memory impairment in offspring through inducing abnormal development of the fetal prefrontal cortex (PFC). Pregnant mice at gestational day 15.5 received 2.5% sevoflurane for 6 h. Learning function of the offspring was evaluated with the Morris water maze test at postnatal day 30. Brain tissues of fetal mice were subjected to immunofluorescence staining to assess differentiation, proliferation, and cell cycle dynamics of the fetal PFC. We found that maternal sevoflurane anesthesia impaired learning ability in offspring through inhibiting deep-layer immature neuron output and neuronal progenitor replication. With the assessment of cell cycle dynamics, we established that these effects were mediated through cell cycle arrest in neural progenitors. Our research has provided insights into the cell cycle-related mechanisms by which maternal sevoflurane exposure can induce neurodevelopmental abnormalities and learning dysfunction and appeals people to consider the neurotoxicity of anesthetics when considering the benefits and risks of nonobstetric surgical procedures.

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“…A developmentally regulated G2 arrest is essential for proper cell fate decisions in sensory organ precursors (SOPs), as disruption of proper Cdk1 activity in SOPs can alter cell division timing and asymmetric cell fate decisions (Fichelson and Gho 2004;Ayeni et al 2016). Consistent with this, we observed that inhibition of Cdk1 activity was sufficient to fully recapitulate the ectopic neuron phenotype in the posterior wing margin, similar to that observed when components of the DREAM or the Myb component of MMB are inhibited (Rovani et al 2012) (Figures 6F and Figure 7, E and F).…”

Section: Nua4 Inhibition Does Not Delay Cell Cycle Exit Through the Pmentioning

confidence: 99%

Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster

Flegel¹,

Grushko²,

Bolin³

et al. 2016

Genetics

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Robust and synchronous repression of E2F-dependent gene expression is critical to the proper timing of cell cycle exit when cells transition to a postmitotic state. Previously NuA4 was suggested to act as a barrier to proliferation in Drosophila by repressing E2F-dependent gene expression. Here we show that NuA4 activity is required for proper cell cycle exit and the repression of cell cycle genes during the transition to a postmitotic state in vivo. However, the delay of cell cycle exit caused by compromising NuA4 is not due to additional proliferation or effects on E2F activity. Instead NuA4 inhibition results in slowed cell cycle progression through late S and G2 phases due to aberrant activation of an intrinsic p53-independent DNA damage response. A reduction in NuA4 function ultimately produces a paradoxical cell cycle gene expression program, where certain cell cycle genes become derepressed in cells that are delayed during the G2 phase of the final cell cycle. Bypassing the G2 delay when NuA4 is inhibited leads to abnormal mitoses and results in severe tissue defects. NuA4 physically and genetically interacts with components of the E2F complex termed Drosophila, Rbf, E2F and Myb/Multi-vulva class B (DREAM/MMB), and modulates a DREAM/MMB-dependent ectopic neuron phenotype in the posterior wing margin. However, this effect is also likely due to the cell cycle delay, as simply reducing Cdk1 is sufficient to generate a similar phenotype. Our work reveals that the major requirement for NuA4 in the cell cycle in vivo is to suppress an endogenous DNA damage response, which is required to coordinate proper S and G2 cell cycle progression with differentiation and cell cycle gene expression.KEYWORDS DNA damage; proliferation; H2Av; cell cycle checkpoint; cell cycle exit A conserved eukaryotic transcriptional oscillator controls cell cycle gene expression in proliferating cells and underlies the well-studied Cyclin/Cdk cell cycle protein oscillator (Orlando et al. 2008;Oikonomou and Cross 2010). In metazoans, this oscillator depends upon transcriptional activation of several hundred cell cycle genes, initiated by E2F transcription factor complexes followed by E2F inhibition (or degradation) (Shibutani et al. 2008;Zielke et al. 2011;Sadasivam and Decaprio 2013). This generates an oscillation of chromatin opening and closing at cell cycle genes that is thought to properly coordinate G1/S and G2/M gene expression as well as the transition to a noncycling state (Litovchick et al. 2007(Litovchick et al. , 2011Forristal et al. 2014). Disruption of this coordination can affect cell cycle progression by causing inappropriate gene expression (Reis and Edgar 2004;Wen et al. 2008;Forristal et al. 2014). While the oscillation of E2F activity is required for robust cell cycle gene expression Korenjak et al. 2012), E2F complexes are not absolutely essential for cell cycle progression or timely cell cycle exit in Drosophila (Frolov et al. 2001(Frolov et al. , 2005. In the absence of E2F activity there must be E2F-independ...

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G2-phase arrest prevents bristle progenitor self-renewal and synchronizes cell divisions with cell fate differentiation

Cited by 17 publications

References 51 publications

Coordinated control of Notch-Delta signalling and cell cycle progression drives lateral inhibition mediated tissue patterning

Coordinated control of Notch-Delta signalling and cell cycle progression drives lateral inhibition mediated tissue patterning

Maternal Sevoflurane Exposure Causes Abnormal Development of Fetal Prefrontal Cortex and Induces Cognitive Dysfunction in Offspring

Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster

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