Cell-Size Control

Amodeo, Amanda A.; Skotheim, Jan M.

doi:10.1101/cshperspect.a019083

Cited by 160 publications

(173 citation statements)

References 119 publications

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“…In other eukaryotes, both G1/S and G2/M are subject to size checkpoints (2,38,39). Cell size and ploidy increase together when the endocycle, which bypasses mitosis, is implemented in A. thaliana sepals (40) and other differentiated tissues or by blocking division with the microtubule inhibitor oryzalin (13), indicating that the trigger for G1/S may affect regulation of the cell size/ ploidy ratio rather than cell size per se (41). Our results indicate that in the SAM, where cells are diploid, G1/S is not triggered by the attainment of a critical size or critical cell size/ploidy ratio, because such regulation would contradict the positive correlations between birth and division sizes (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…How this sistercell growth heterogeneity can be integrated with the report that growth heterogeneity is induced by neighbor interactions (30) is a future challenge. A feasible mechanism features a master regulator of growth with the following dynamics: (i) its concentration is fixed through the cell cycle and is proportional to the per unit size growth rate; (ii) upon mitosis, the growth regulator is degraded or synthesized to attain a specific concentration; and (iii) upon division, the regulator is partitioned equally in number between the two daughters perhaps via titration against DNA (41). Such a mechanism would impart a higher concentration of the master regulator to the smaller sister.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche

Willis

Refahi

Wightman

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

180

217

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Cell size and growth kinetics are fundamental cellular properties with important physiological implications. Classical studies on yeast, and recently on bacteria, have identified rules for cell size regulation in single cells, but in the more complex environment of multicellular tissues, data have been lacking. In this study, to characterize cell size and growth regulation in a multicellular context, we developed a 4D imaging pipeline and applied it to track and quantify epidermal cells over 3-4 d in Arabidopsis thaliana shoot apical meristems. We found that a cell size checkpoint is not the trigger for G2/M or cytokinesis, refuting the unexamined assumption that meristematic cells trigger cell cycle phases upon reaching a critical size. Our data also rule out models in which cells undergo G2/M at a fixed time after birth, or by adding a critical size increment between G2/M transitions. Rather, cell size regulation was intermediate between the critical size and critical increment paradigms, meaning that cell size fluctuations decay by ∼75% in one generation compared with 100% (critical size) and 50% (critical increment). Notably, this behavior was independent of local cell-cell contact topologies and of position within the tissue. Cells grew exponentially throughout the first >80% of the cell cycle, but following an asymmetrical division, the small daughter grew at a faster exponential rate than the large daughter, an observation that potentially challenges present models of growth regulation. These growth and division behaviors place strong constraints on quantitative mechanistic descriptions of the cell cycle and growth control.cell size | cell growth | cell cycle | homeostasis | plant stem cells H ow cells coordinate growth and division to achieve a particular cell size remains a fundamental question in biology. Our understanding of this basic property of cells is limited, in part, by the lack of quantitative data on cellular growth and size kinetics over multiple generations, especially in higher eukaryotes (1). Classical studies of cell size homeostasis focused on whether division occurred upon reaching a critical size or after a fixed time period has elapsed (2, 3). However, time-lapse studies of single-celled organisms spanning a range of bacteria (4-7) and the yeast Saccharomyces cerevisiae (8) have recently indicated that cell size is regulated by the addition of a fixed volume increment between divisions. Identification of the size regulation behavior constrains the set of feasible molecular scenarios for how growth and division are coordinated with the cell cycle (8-10). In multicellular tissues, the loss of growth and division/cell cycle coordination could have an impact on the organism's development, yet, to the best of our knowledge, cell growth and size kinetics have never before been measured over generations in a tissue context. The experimental challenges are particularly acute because interdivision times are often on the order of tens of hours, cells have a diversity of shapes necessitating di...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche

Willis

Refahi

Wightman

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

180

217

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“…Once a threshold amount of DNA is reached, there are insufficient numbers of MBT inhibitory molecules to sufficiently bind all DNA, thus leading to induction of the MBT. 122,124 Several potential limiting DNA binding factors have been identified: histones, 125 phosphatase PP2A, 126 and DNA replication initiation factors. 127 Another protein that acts though a limiting titration mechanism is RAD18, a ubiquitin ligase responsible for monoubiquitination of PCNA.…”

Section: Nuclear Size In Embryonic Developmentmentioning

confidence: 99%

Recent advances in understanding nuclear size and shape

Mukherjee

Chen

Levy

2016

Nucleus

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Size and shape are important aspects of nuclear structure. While normal cells maintain nuclear size within a defined range, altered nuclear size and shape are associated with a variety of diseases. It is unknown if altered nuclear morphology contributes to pathology, and answering this question requires a better understanding of the mechanisms that control nuclear size and shape. In this review, we discuss recent advances in our understanding of the mechanisms that regulate nuclear morphology, focusing on nucleocytoplasmic transport, nuclear lamins, the endoplasmic reticulum, the cell cycle, and potential links between nuclear size and size regulation of other organelles. We then discuss the functional significance of nuclear morphology in the context of early embryonic development. Looking toward the future, we review new experimental approaches that promise to provide new insights into mechanisms of nuclear size control, in particular microfluidic-based technologies, and discuss how altered nuclear morphology might impact chromatin organization and physiology of diseased cells.

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“…Thus, we define scaling mechanisms as those that directly regulate organelle size (or capacity) in response to changes in cell size and distinguish these from size-control mechanisms, which are the subject of reviews elsewhere in this collection (see also Amodeo and Skotheim 2015;Levy and Heald 2015;Marshall 2015;Mitchison et al 2015). Although scaling and size-control mechanisms are distinct, they are often linked.…”

mentioning

confidence: 99%

Intracellular Scaling Mechanisms

Reber

Goehring

2015

Cold Spring Harb Perspect Biol

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Organelle function is often directly related to organelle size. However, it is not necessarily absolute size but the organelle-to-cell-size ratio that is critical. Larger cells generally have increased metabolic demands, must segregate DNA over larger distances, and require larger cytokinetic rings to divide. Thus, organelles often must scale to the size of the cell. The need for scaling is particularly acute during early development during which cell size can change rapidly. Here, we highlight scaling mechanisms for cellular structures as diverse as centrosomes, nuclei, and the mitotic spindle, and distinguish them from more general mechanisms of size control. In some cases, scaling is a consequence of the underlying mechanism of organelle size control. In others, size-control mechanisms are not obviously related to cell size, implying that scaling results indirectly from cell-size-dependent regulation of sizecontrol mechanisms.

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Cell-Size Control

Cited by 160 publications

References 119 publications

Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche

Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche

Recent advances in understanding nuclear size and shape

Intracellular Scaling Mechanisms

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