Stochastic dynamics of cell lineage in tissue homeostasis

Qiu, Yuchi; Chen, Weitao; Nie, Qing

doi:10.3934/dcdsb.2018339

“…Intuitively, the underlying mechanism of noise-induced switching can be regarded as a battle between the extrinsic noise and the intrinsic noise. Such noise battle has also been reported in the stratified epithelial tissue maintenance: a balanced level of different noises is essential to homeostasis [89]. Cells may tune both intrinsic and extrinsic noise within certain ranges, then an optimal levels of these two noise can be achieved to get robust and precise spatial patterns.…”

Section: Utilizing Gene Expression Noise To Battle Noise In Morphogenmentioning

confidence: 82%

Noise control and utility: From regulatory network to spatial patterning

Nie

¹

,

Qiao

²

,

Qiu

³

et al. 2020

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Stochasticity (or noise) at cellular and molecular levels has been observed extensively as a universal feature for living systems. However, how living systems deal with noise while performing desirable biological functions remains a major mystery. Regulatory network configurations, such as their topology and timescale, are shown to be critical in attenuating noise, and noise is also found to facilitate cell fate decision. Here we review major recent findings on noise attenuation through regulatory control, the benefit of noise via noise-induced cellular plasticity during developmental patterning, and summarize key principles underlying noise control. 2 Nie Q et al. Sci China Math studies investigate how to control or utilize noise in living systems [7,10,[10][11][12][13][14][15][16][17][18]. While noise may induce heterogeneity within the cell population, contributing to diversity in cell fate choice [19][20][21], it usually causes uncertainty in information transmission in the cell and impairs robustness of cellular functions, which is one of the main reasons for the difficulty in robust circuit functions [4,22]. A natural question at hand is how cells deal with noise effectively.Since cellular functions, such as bistability, oscillation and adaptation, have been found to link to regulatory network architectures [23], the network property is naturally important in noise control [18,[24][25][26][27][28][29][30][31]. What are basic constraints on the regulatory networks for noise attenuation? How noise is controlled in function-specific systems, such as adaptive systems or oscillatory systems? In addition, can noise be utilized to achieve specific biological functions? How does noise affect spatial organization and morphogen-mediated patterning? How can a precise and robust readout be generated from the noisy spatial morphogen gradient?In this work, we first review major noise attenuation mechanisms in regulatory networks, and then explore key strategies to combat noise in morphogens during spatial patterning. We conclude by summarizing the major mechanisms in noise control.

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“…Interestingly, noise in gene expression can counteract other stochastic effects (e.g. noise in morphogen levels) to improve pattern formation precision [ 17 , 33 ]. In addition to these molecular strategies, pattern precision can be improved through cellular strategies, such as cell sorting driven by cell-cell interactions [ 16 , 20 ] or “community effects” of signals from adjacent cells [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Multiple morphogens and rapid elongation promote segmental patterning during development

Qiu

¹

,

Fung

²

,

Schilling

³

et al. 2021

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The vertebrate hindbrain is segmented into rhombomeres (r) initially defined by distinct domains of gene expression. Previous studies have shown that noise-induced gene regulation and cell sorting are critical for the sharpening of rhombomere boundaries, which start out rough in the forming neural plate (NP) and sharpen over time. However, the mechanisms controlling simultaneous formation of multiple rhombomeres and accuracy in their sizes are unclear. We have developed a stochastic multiscale cell-based model that explicitly incorporates dynamic morphogenetic changes (i.e. convergent-extension of the NP), multiple morphogens, and gene regulatory networks to investigate the formation of rhombomeres and their corresponding boundaries in the zebrafish hindbrain. During pattern initiation, the short-range signal, fibroblast growth factor (FGF), works together with the longer-range morphogen, retinoic acid (RA), to specify all of these boundaries and maintain accurately sized segments with sharp boundaries. At later stages of patterning, we show a nonlinear change in the shape of rhombomeres with rapid left-right narrowing of the NP followed by slower dynamics. Rapid initial convergence improves boundary sharpness and segment size by regulating cell sorting and cell fate both independently and coordinately. Overall, multiple morphogens and tissue dynamics synergize to regulate the sizes and boundaries of multiple segments during development.

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“…Interestingly, noise in gene expression can counteract other stochastic effects (e.g. noise in morphogen levels) to improve pattern formation precision [17,33].…”

Section: Introductionmentioning

confidence: 99%

Multiple morphogens and rapid elongation promote segmental patterning during development

Qiu

¹

,

Fung²,

Schilling³

et al. 2021

Preprint

Self Cite

1

0

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The vertebrate hindbrain is segmented into rhombomeres (r) initially defined by distinct domains of gene expression. Previous studies have shown that noise-induced gene regulation and cell sorting are critical for the sharpening of rhombomere boundaries, which start out rough in the forming neural plate (NP) and sharpen over time. However, the mechanisms controlling simultaneous formation of multiple rhombomeres and accuracy in their sizes are unclear. We have developed a stochastic multiscale cell-based model that explicitly incorporates dynamic morphogenetic changes (i.e. convergent-extension of the NP), multiple morphogens, and gene regulatory networks to investigate the formation of rhombomeres and their corresponding boundaries in the zebrafish hindbrain. During pattern initiation, the short-range signal, fibroblast growth factor (FGF), works together with the longer-range morphogen, retinoic acid (RA), to specify all of these boundaries and maintain accurately-sized segments with sharp boundaries. At later stages of patterning, we show a nonlinear change in the shape of rhombomeres with rapid left-right narrowing of the NP followed by slower dynamics. Rapid initial convergence improves boundary sharpness and segment size by regulating cell sorting and cell fate both independently and coordinately. Overall, multiple morphogens and tissue dynamics synergize to regulate the sizes and boundaries of multiple segments during development.Author SummaryIn segmental pattern formation, chemical gradients control gene expression in a concentration-dependent manner to specify distinct gene expression domains. Despite the stochasticity inherent to such biological processes, precise and accurate borders form between segmental gene expression domains. Previous work has revealed synergy between gene regulation and cell sorting in sharpening borders that are initially rough. However, it is still poorly understood how size and boundary sharpness ofmultiplesegments are regulated in a tissue that changes dramatically in its morphology as the embryo develops. Here we develop a stochastic multiscale cell-base model to investigate these questions. Two novel strategies synergize to promote accurate segment formation, a combination of long- and short-range morphogens plus rapid tissue convergence, with one responsible for pattern initiation and the other enabling pattern refinement.

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Stochastic dynamics of cell lineage in tissue homeostasis

Cited by 4 publications

References 50 publications

Noise control and utility: From regulatory network to spatial patterning

Noise control and utility: From regulatory network to spatial patterning

Multiple morphogens and rapid elongation promote segmental patterning during development

Multiple morphogens and rapid elongation promote segmental patterning during development

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