Publications by authors named "Henrik Jönsson"

74 Publications

Molecular mechanism of cytokinin-activated cell division in .

Science 2021 03 25;371(6536):1350-1355. Epub 2021 Feb 25.

Sainsbury Laboratory, University of Cambridge, Bateman Street, Cambridge CB2 1LR, UK.

Mitogens trigger cell division in animals. In plants, cytokinins, a group of phytohormones derived from adenine, stimulate cell proliferation. Cytokinin signaling is initiated by membrane-associated histidine kinase receptors and transduced through a phosphorelay system. We show that in the shoot apical meristem (SAM), cytokinin regulates cell division by promoting nuclear shuttling of Myb-domain protein 3R4 (MYB3R4), a transcription factor that activates mitotic gene expression. Newly synthesized MYB3R4 protein resides predominantly in the cytoplasm. At the G2-to-M transition, rapid nuclear accumulation of MYB3R4-consistent with an associated transient peak in cytokinin concentration-feeds a positive feedback loop involving importins and initiates a transcriptional cascade that drives mitosis and cytokinesis. An engineered nuclear-restricted MYB3R4 mimics the cytokinin effects of enhanced cell proliferation and meristem growth.
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http://dx.doi.org/10.1126/science.abe2305DOI Listing
March 2021

A multiscale analysis of early flower development in Arabidopsis provides an integrated view of molecular regulation and growth control.

Dev Cell 2021 Feb;56(4):540-556.e8

Laboratoire RDP, Université de Lyon 1, ENS-Lyon, INRAE, CNRS, UCBL, 69364 Lyon, France. Electronic address:

We have analyzed the link between the gene regulation and growth during the early stages of flower development in Arabidopsis. Starting from time-lapse images, we generated a 4D atlas of early flower development, including cell lineage, cellular growth rates, and the expression patterns of regulatory genes. This information was introduced in MorphoNet, a web-based platform. Using computational models, we found that the literature-based molecular network only explained a minority of the gene expression patterns. This was substantially improved by adding regulatory hypotheses for individual genes. Correlating growth with the combinatorial expression of multiple regulators led to a set of hypotheses for the action of individual genes in morphogenesis. This identified the central factor LEAFY as a potential regulator of heterogeneous growth, which was supported by quantifying growth patterns in a leafy mutant. By providing an integrated view, this atlas should represent a fundamental step toward mechanistic models of flower development.
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http://dx.doi.org/10.1016/j.devcel.2021.01.019DOI Listing
February 2021

Tissue folding at the organ-meristem boundary results in nuclear compression and chromatin compaction.

Proc Natl Acad Sci U S A 2021 Feb;118(8)

Laboratoire de Reproduction et Développement des Plantes, Université de Lyon, Université Claude Bernard Lyon 1, ENS de Lyon, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE), CNRS, 69364 Lyon Cedex 07, France;

Artificial mechanical perturbations affect chromatin in animal cells in culture. Whether this is also relevant to growing tissues in living organisms remains debated. In plants, aerial organ emergence occurs through localized outgrowth at the periphery of the shoot apical meristem, which also contains a stem cell niche. Interestingly, organ outgrowth has been proposed to generate compression in the saddle-shaped organ-meristem boundary domain. Yet whether such growth-induced mechanical stress affects chromatin in plant tissues is unknown. Here, by imaging the nuclear envelope in vivo over time and quantifying nucleus deformation, we demonstrate the presence of active nuclear compression in that domain. We developed a quantitative pipeline amenable to identifying a subset of very deformed nuclei deep in the boundary and in which nuclei become gradually narrower and more elongated as the cell contracts transversely. In this domain, we find that the number of chromocenters is reduced, as shown by chromatin staining and labeling, and that the expression of linker histone H1.3 is induced. As further evidence of the role of forces on chromatin changes, artificial compression with a MicroVice could induce the ectopic expression of H1.3 in the rest of the meristem. Furthermore, while the methylation status of chromatin was correlated with nucleus deformation at the meristem boundary, such correlation was lost in the mutant. Altogether, we reveal that organogenesis in plants generates compression that is able to have global effects on chromatin in individual cells.
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http://dx.doi.org/10.1073/pnas.2017859118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923354PMC
February 2021

Limits and Constraints on Mechanisms of Cell-Cycle Regulation Imposed by Cell Size-Homeostasis Measurements.

Cell Rep 2020 08;32(6):107992

Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address:

High-throughput imaging has led to an explosion of observations about cell-size homeostasis across the kingdoms of life. Among bacteria, "adder" behavior-in which a constant size increment appears to be added during each cell cycle-is ubiquitous, while various eukaryotes show other size-homeostasis behaviors. Since interactions between cell-cycle progression and growth ultimately determine such behaviors, we developed a general model of cell-cycle regulation. Our analyses reveal a range of scenarios that are plausible but fail to regulate cell size, indicating that mechanisms of cell-cycle regulation are stringently limited by size-control requirements, and possibly why certain cell-cycle features are strongly conserved. Cell-cycle features can play unintuitive roles in altering size-homeostasis behaviors: noisy regulator production can enhance adder behavior, while Whi5-like inhibitor dilutors respond sensitively to perturbations to G2/M control and noisy G1/S checkpoints. Our model thus provides holistic insights into the mechanistic implications of size-homeostasis experimental measurements.
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http://dx.doi.org/10.1016/j.celrep.2020.107992DOI Listing
August 2020

Cytoskeletal organization in isolated plant cells under geometry control.

Proc Natl Acad Sci U S A 2020 07 8;117(29):17399-17408. Epub 2020 Jul 8.

The Sainsbury Laboratory, University of Cambridge, Cambridge CB2 1LR, United Kingdom;

The cytoskeleton plays a key role in establishing robust cell shape. In animals, it is well established that cell shape can also influence cytoskeletal organization. Cytoskeletal proteins are well conserved between animal and plant kingdoms; nevertheless, because plant cells exhibit major structural differences to animal cells, the question arises whether the plant cytoskeleton also responds to geometrical cues. Recent numerical simulations predicted that a geometry-based rule is sufficient to explain the microtubule (MT) organization observed in cells. Due to their high flexural rigidity and persistence length of the order of a few millimeters, MTs are rigid over cellular dimensions and are thus expected to align along their long axis if constrained in specific geometries. This hypothesis remains to be tested Here, we explore the relative contribution of geometry to the final organization of actin and MT cytoskeletons in single plant cells of We show that the cytoskeleton aligns with the long axis of the cells. We find that actin organization relies on MTs but not the opposite. We develop a model of self-organizing MTs in three dimensions, which predicts the importance of MT severing, which we confirm experimentally. This work is a first step toward assessing quantitatively how cellular geometry contributes to the control of cytoskeletal organization in living plant cells.
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http://dx.doi.org/10.1073/pnas.2003184117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382239PMC
July 2020

It's about time: Analysing simplifying assumptions for modelling multi-step pathways in systems biology.

PLoS Comput Biol 2020 06 29;16(6):e1007982. Epub 2020 Jun 29.

The Sainsbury Laboratory, University of Cambridge, Cambridge, United Kingdom.

Thoughtful use of simplifying assumptions is crucial to make systems biology models tractable while still representative of the underlying biology. A useful simplification can elucidate the core dynamics of a system. A poorly chosen assumption can, however, either render a model too complicated for making conclusions or it can prevent an otherwise accurate model from describing experimentally observed dynamics. Here, we perform a computational investigation of sequential multi-step pathway models that contain fewer pathway steps than the system they are designed to emulate. We demonstrate when such models will fail to reproduce data and how detrimental truncation of a pathway leads to detectable signatures in model dynamics and its optimised parameters. An alternative assumption is suggested for simplifying such pathways. Rather than assuming a truncated number of pathway steps, we propose to use the assumption that the rates of information propagation along the pathway is homogeneous and, instead, letting the length of the pathway be a free parameter. We first focus on linear pathways that are sequential and have first-order kinetics, and we show how this assumption results in a three-parameter model that consistently outperforms its truncated rival and a delay differential equation alternative in recapitulating observed dynamics. We then show how the proposed assumption allows for similarly terse and effective models of non-linear pathways. Our results provide a foundation for well-informed decision making during model simplifications.
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http://dx.doi.org/10.1371/journal.pcbi.1007982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351226PMC
June 2020

Auxin transport model for leaf venation.

Proc Math Phys Eng Sci 2019 Nov 20;475(2231):20190015. Epub 2019 Nov 20.

Mathematics, CEMSE, KAUST, Thuwal 23955-6900, KSA.

The plant hormone auxin controls many aspects of the development of plants. One striking dynamical feature is the self-organization of leaf venation patterns which is driven by high levels of auxin within vein cells. The auxin transport is mediated by specialized membrane-localized proteins. Many venation models have been based on polarly localized efflux-mediator proteins of the PIN family. Here, we investigate a modelling framework for auxin transport with a positive feedback between auxin fluxes and transport capacities that are not necessarily polar, i.e. directional across a cell wall. Our approach is derived from a discrete graph-based model for biological transportation networks, where cells are represented by graph nodes and intercellular membranes by edges. The edges are not oriented and the direction of auxin flow is determined by its concentration gradient along the edge. We prove global existence of solutions to the model and the validity of Murray's Law for its steady states. Moreover, we demonstrate with numerical simulations that the model is able connect an auxin source-sink pair with a mid-vein and that it can also produce branching vein patterns. A significant innovative aspect of our approach is that it allows the passage to a formal macroscopic limit which can be extended to include network growth. We perform mathematical analysis of the macroscopic formulation, showing the global existence of weak solutions for an appropriate parameter range.
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http://dx.doi.org/10.1098/rspa.2019.0015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894547PMC
November 2019

Mechanical Asymmetry of the Cell Wall Predicts Changes in Pavement Cell Geometry.

Dev Cell 2019 07;50(1):9-10

Umeå Plant Science Centre (UPSC), Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, 901 83 Umeå, Sweden. Electronic address:

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http://dx.doi.org/10.1016/j.devcel.2019.06.002DOI Listing
July 2019

The rise of a forgotten model.

Authors:
Henrik Jönsson

Nat Rev Mol Cell Biol 2019 08;20(8):455

Sainsbury Laboratory, University of Cambridge, Cambridge, UK.

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http://dx.doi.org/10.1038/s41580-019-0144-0DOI Listing
August 2019

Quantitative analysis of auxin sensing in leaf primordia argues against proposed role in regulating leaf dorsoventrality.

Elife 2019 01 22;8. Epub 2019 Jan 22.

School of Life and Environmental Sciences, University of Sydney, Sydney, Australia.

Dorsoventrality in leaves has been shown to depend on the pre-patterned expression of KANADI and HD-ZIPIII genes within the plant shoot apical meristem (SAM). However, it has also been proposed that asymmetric auxin levels within initiating leaves help establish leaf polarity, based in part on observations of the DII auxin sensor. By analyzing and quantifying the expression of the R2D2 auxin sensor, we find that there is no obvious asymmetry in auxin levels during Arabidopsis leaf development. We further show that the mDII control sensor also exhibits an asymmetry in expression in developing leaf primordia early on, while it becomes more symmetric at a later developmental stage as reported previously. Together with other recent findings, our results argue against the importance of auxin asymmetry in establishing leaf polarity.
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http://dx.doi.org/10.7554/eLife.39298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6342526PMC
January 2019

Crack nucleation and propagation in microcrystalline-cellulose based granules subject to uniaxial and triaxial load.

Int J Pharm 2019 Mar 29;559:130-137. Epub 2018 Dec 29.

Department of Pharmacy and the Swedish Drug Delivery Forum (SDDF), Uppsala University, Box 580, 751 23 Uppsala, Sweden.

Cracking patterns in four kinds of granules, based on the common pharmaceutical excipient microcrystalline cellulose (MCC) and subject to compressive load, were examined. The initial pore structure and the location of initial failure under uniaxial compression were assessed using X-ray micro-computed tomography, whereas contact force development and onset of cracking under more complex compressive load were examined using a triaxial testing apparatus. Smoothed particle hydrodynamics (SPH) simulations were employed for numerical analysis of the stress distributions prior to cracking. For granules subject to uniaxial compression, initial cracking always occurred along the meridian and the precise location of the crack depended on the pore structure. Likewise, for granules subject to triaxial compression, the fracture plane of the primary crack was generally parallel to the dominant loading direction. The occurrence of cracking was highly dependent on the triaxiality ratio, i.e. the ratio between the punch displacements in the secondary and dominant loading directions. Compressive stresses in the lateral directions, induced by triaxial compression, prevented crack opening and fragmentation of the granule, something that could be verified by simulations. These results provide corroboration as well as further insights into previously observed differences between confined and unconfined compression of granular media.
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http://dx.doi.org/10.1016/j.ijpharm.2018.12.064DOI Listing
March 2019

Anisotropic growth is achieved through the additive mechanical effect of material anisotropy and elastic asymmetry.

Elife 2018 09 18;7. Epub 2018 Sep 18.

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.

Fast directional growth is a necessity for the young seedling; after germination, it needs to quickly penetrate the soil to begin its autotrophic life. In most dicot plants, this rapid escape is due to the anisotropic elongation of the hypocotyl, the columnar organ between the root and the shoot meristems. Anisotropic growth is common in plant organs and is canonically attributed to cell wall anisotropy produced by oriented cellulose fibers. Recently, a mechanism based on asymmetric pectin-based cell wall elasticity has been proposed. Here we present a harmonizing model for anisotropic growth control in the dark-grown hypocotyl: basic anisotropic information is provided by cellulose orientation) and additive anisotropic information is provided by pectin-based elastic asymmetry in the epidermis. We quantitatively show that hypocotyl elongation is anisotropic starting at germination. We present experimental evidence for pectin biochemical differences and wall mechanics providing important growth regulation in the hypocotyl. Lastly, our in silico modelling experiments indicate an additive collaboration between pectin biochemistry and cellulose orientation in promoting anisotropic growth.
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http://dx.doi.org/10.7554/eLife.38161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143341PMC
September 2018

The interaction of transcription factors controls the spatial layout of plant aerial stem cell niches.

NPJ Syst Biol Appl 2018 6;4:36. Epub 2018 Sep 6.

1Sainsbury Laboratory, University of Cambridge, Bateman Street, Cambridge, CB2 1LR UK.

The plant shoot apical meristem holds a stem cell niche from which all aerial organs originate. Using a computational approach we show that a mixture of monomers and heterodimers of the transcription factors WUSCHEL and HAIRY MERISTEM is sufficient to pattern the stem cell niche, and predict that immobile heterodimers form a regulatory "pocket" surrounding the stem cells. The model achieves to reproduce an array of perturbations, including mutants and tissue size modifications. We also show its ability to reproduce the recently observed dynamical shift of the stem cell niche during the development of an axillary meristem. The work integrates recent experimental results to answer the longstanding question of how the asymmetry of expression between the stem cell marker and its activator is achieved, and recent findings of plasticity in the system.
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http://dx.doi.org/10.1038/s41540-018-0072-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127332PMC
September 2018

The self-organization of plant microtubules inside the cell volume yields their cortical localization, stable alignment, and sensitivity to external cues.

PLoS Comput Biol 2018 02 20;14(2):e1006011. Epub 2018 Feb 20.

Reproduction et Développement des Plantes, Univ. Lyon, ENS de Lyon, UCB Lyon 1, CNRS, INRA, F-69364 Lyon, France.

Many cell functions rely on the ability of microtubules to self-organize as complex networks. In plants, cortical microtubules are essential to determine cell shape as they guide the deposition of cellulose microfibrils, and thus control mechanical anisotropy of the cell wall. Here we analyze how, in turn, cell shape may influence microtubule behavior. Building upon previous models that confined microtubules to the cell surface, we introduce an agent model of microtubules enclosed in a three-dimensional volume. We show that the microtubule network has spontaneous aligned configurations that could explain many experimental observations without resorting to specific regulation. In particular, we find that the preferred cortical localization of microtubules emerges from directional persistence of the microtubules, and their interactions with each other and with the stiff wall. We also identify microtubule parameters that seem relatively insensitive to cell shape, such as length or number. In contrast, microtubule array anisotropy depends on local curvature of the cell surface and global orientation follows robustly the longest axis of the cell. Lastly, we find that geometric cues may be overcome, as the network is capable of reorienting toward weak external directional cues. Altogether our simulations show that the microtubule network is a good transducer of weak external polarity, while at the same time, easily reaching stable global configurations.
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http://dx.doi.org/10.1371/journal.pcbi.1006011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834207PMC
February 2018

Nitrate modulates stem cell dynamics in shoot meristems through cytokinins.

Proc Natl Acad Sci U S A 2018 02 23;115(6):1382-1387. Epub 2018 Jan 23.

Sainsbury Laboratory, University of Cambridge, CB2 1LR Cambridge, United Kingdom;

The shoot apical meristem (SAM) is responsible for the generation of all the aerial parts of plants. Given its critical role, dynamical changes in SAM activity should play a central role in the adaptation of plant architecture to the environment. Using quantitative microscopy, grafting experiments, and genetic perturbations, we connect the plant environment to the SAM by describing the molecular mechanism by which cytokinins signal the level of nutrient availability to the SAM. We show that a systemic signal of cytokinin precursors mediates the adaptation of SAM size and organogenesis rate to the availability of mineral nutrients by modulating the expression of , a key regulator of stem cell homeostasis. In time-lapse experiments, we further show that this mechanism allows meristems to adapt to rapid changes in nitrate concentration, and thereby modulate their rate of organ production to the availability of mineral nutrients within a few days. Our work sheds light on the role of the stem cell regulatory network by showing that it not only maintains meristem homeostasis but also allows plants to adapt to rapid changes in the environment.
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http://dx.doi.org/10.1073/pnas.1718670115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819446PMC
February 2018

Mechanochemical Polarization of Contiguous Cell Walls Shapes Plant Pavement Cells.

Dev Cell 2017 11;43(3):290-304.e4

Umeå Plant Science Centre (UPSC), Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, 901 83 Umeå, Sweden. Electronic address:

The epidermis of aerial plant organs is thought to be limiting for growth, because it acts as a continuous load-bearing layer, resisting tension. Leaf epidermis contains jigsaw puzzle piece-shaped pavement cells whose shape has been proposed to be a result of subcellular variations in expansion rate that induce local buckling events. Paradoxically, such local compressive buckling should not occur given the tensile stresses across the epidermis. Using computational modeling, we show that the simplest scenario to explain pavement cell shapes within an epidermis under tension must involve mechanical wall heterogeneities across and along the anticlinal pavement cell walls between adjacent cells. Combining genetics, atomic force microscopy, and immunolabeling, we demonstrate that contiguous cell walls indeed exhibit hybrid mechanochemical properties. Such biochemical wall heterogeneities precede wall bending. Altogether, this provides a possible mechanism for the generation of complex plant cell shapes.
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http://dx.doi.org/10.1016/j.devcel.2017.10.017DOI Listing
November 2017

Cell type boundaries organize plant development.

Elife 2017 09 12;6. Epub 2017 Sep 12.

European Molecular Biology Laboratory, Heidelberg, Germany.

In plants the dorsoventral boundary of leaves defines an axis of symmetry through the centre of the organ separating the top (dorsal) and bottom (ventral) tissues. Although the positioning of this boundary is critical for leaf morphogenesis, how the boundary is established and how it influences development remains unclear. Using live-imaging and perturbation experiments we show that leaf orientation, morphology and position are pre-patterned by HD-ZIPIII and KAN gene expression in the shoot, leading to a model in which dorsoventral genes coordinate to regulate plant development by localizing auxin response between their expression domains. However we also find that auxin levels feedback on dorsoventral patterning by spatially organizing HD-ZIPIII and KAN expression in the shoot periphery. By demonstrating that the regulation of these genes by auxin also governs their response to wounds, our results also provide a parsimonious explanation for the influence of wounds on leaf dorsoventrality.
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http://dx.doi.org/10.7554/eLife.27421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5617630PMC
September 2017

Different reprogramming propensities in plants and mammals: Are small variations in the core network wirings responsible?

PLoS One 2017 6;12(4):e0175251. Epub 2017 Apr 6.

Computational Biology and Biological Physics, Lund University, Lund, Sweden.

Although the plant and animal kingdoms were separated more than 1,6 billion years ago, multicellular development is for both guided by similar transcriptional, epigenetic and posttranscriptional machinery. One may ask to what extent there are similarities and differences in the gene regulation circuits and their dynamics when it comes to important processes like stem cell regulation. The key players in mouse embryonic stem cells governing pluripotency versus differentiation are Oct4, Sox2 and Nanog. Correspondingly, the WUSCHEL and CLAVATA3 genes represent a core in the Shoot Apical Meristem regulation for plants. In addition, both systems have designated genes that turn on differentiation. There is very little molecular homology between mammals and plants for these core regulators. Here, we focus on functional homologies by performing a comparison between the circuitry connecting these players in plants and animals and find striking similarities, suggesting that comparable regulatory logics have been evolved for stem cell regulation in both kingdoms. From in silico simulations we find similar differentiation dynamics. Further when in the differentiated state, the cells are capable of regaining the stem cell state. We find that the propensity for this is higher for plants as compared to mammalians. Our investigation suggests that, despite similarity in core regulatory networks, the dynamics of these can contribute to plant cells being more plastic than mammalian cells, i.e. capable to reorganize from single differentiated cells to whole plants-reprogramming. The presence of an incoherent feed-forward loop in the mammalian core circuitry could be the origin of the different reprogramming behaviour.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175251PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383272PMC
September 2017

Fluctuations of the transcription factor ATML1 generate the pattern of giant cells in the sepal.

Elife 2017 02 1;6. Epub 2017 Feb 1.

Weill Institute for Cell and Molecular Biology, Cornell University, , United States.

Multicellular development produces patterns of specialized cell types. Yet, it is often unclear how individual cells within a field of identical cells initiate the patterning process. Using live imaging, quantitative image analyses and modeling, we show that during sepal development, fluctuations in the concentration of the transcription factor ATML1 pattern a field of identical epidermal cells to differentiate into giant cells interspersed between smaller cells. We find that ATML1 is expressed in all epidermal cells. However, its level fluctuates in each of these cells. If ATML1 levels surpass a threshold during the G2 phase of the cell cycle, the cell will likely enter a state of endoreduplication and become giant. Otherwise, the cell divides. Our results demonstrate a fluctuation-driven patterning mechanism for how cell fate decisions can be initiated through a random yet tightly regulated process.
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http://dx.doi.org/10.7554/eLife.19131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333958PMC
February 2017

I: Biomarker quantification in fish exposed to crude oil as input to species sensitivity distributions and threshold values for environmental monitoring.

Mar Environ Res 2017 Apr 20;125:10-24. Epub 2016 Dec 20.

IRIS - International Research Institute of Stavanger, P.O. Box 8046, N-4068, Stavanger, Norway; Faculty of Science and Technology, Department of Mathematics and Natural Science, University of Stavanger, N-4036 Stavanger, Norway.

The aim of this study was to determine a suitable set of biomarker based methods for environmental monitoring in sub-arctic and temperate offshore areas using scientific knowledge on the sensitivity of fish species to dispersed crude oil. Threshold values for environmental monitoring and risk assessment were obtained based on a quantitative comparison of biomarker responses. Turbot, halibut, salmon and sprat were exposed for up to 8 weeks to five different sub-lethal concentrations of dispersed crude oil. Biomarkers assessing PAH metabolites, oxidative stress, detoxification system I activity, genotoxicity, immunotoxicity, endocrine disruption, general cellular stress and histological changes were measured. Results showed that PAH metabolites, CYP1A/EROD, DNA adducts and histopathology rendered the most robust results across the different fish species, both in terms of sensitivity and dose-responsiveness. The reported results contributed to forming links between biomonitoring and risk assessment procedures by using biomarker species sensitivity distributions.
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http://dx.doi.org/10.1016/j.marenvres.2016.12.002DOI Listing
April 2017

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

Proc Natl Acad Sci U S A 2016 12 5;113(51):E8238-E8246. Epub 2016 Dec 5.

The Sainsbury Laboratory, University of Cambridge, Cambridge CB2 1LR, United Kingdom;

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.
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http://dx.doi.org/10.1073/pnas.1616768113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187701PMC
December 2016

A continuous growth model for plant tissue.

Phys Biol 2016 11 15;13(6):065002. Epub 2016 Nov 15.

Computational Biology & Biological Physics, Lund University, Sölvegatan 14A, SE-223 62 Lund, Sweden.

Morphogenesis in plants and animals involves large irreversible deformations. In plants, the response of the cell wall material to internal and external forces is determined by its mechanical properties. An appropriate model for plant tissue growth must include key features such as anisotropic and heterogeneous elasticity and cell dependent evaluation of mechanical variables such as turgor pressure, stress and strain. In addition, a growth model needs to cope with cell divisions as a necessary part of the growth process. Here we develop such a growth model, which is capable of employing not only mechanical signals but also morphogen signals for regulating growth. The model is based on a continuous equation for updating the resting configuration of the tissue. Simultaneously, material properties can be updated at a different time scale. We test the stability of our model by measuring convergence of growth results for a tissue under the same mechanical and material conditions but with different spatial discretization. The model is able to maintain a strain field in the tissue during re-meshing, which is of particular importance for modeling cell division. We confirm the accuracy of our estimations in two and three-dimensional simulations, and show that residual stresses are less prominent if strain or stress is included as input signal to growth. The approach results in a model implementation that can be used to compare different growth hypotheses, while keeping residual stresses and other mechanical variables updated and available for feeding back to the growth and material properties.
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http://dx.doi.org/10.1088/1478-3975/13/6/065002DOI Listing
November 2016

A Model Analysis of Mechanisms for Radial Microtubular Patterns at Root Hair Initiation Sites.

Front Plant Sci 2016 28;7:1560. Epub 2016 Oct 28.

Computational Biology and Biological Physics, Department of Astronomy and Theoretical Physics, Lund UniversityLund, Sweden; Sainsbury Laboratory, University of CambridgeCambridge, UK; Department of Applied Mathematics and Theoretical Physics, University of CambridgeCambridge, UK.

Plant cells have two main modes of growth generating anisotropic structures. Diffuse growth where whole cell walls extend in specific directions, guided by anisotropically positioned cellulose fibers, and tip growth, with inhomogeneous addition of new cell wall material at the tip of the structure. Cells are known to regulate these processes via molecular signals and the cytoskeleton. Mechanical stress has been proposed to provide an input to the positioning of the cellulose fibers via cortical microtubules in diffuse growth. In particular, a stress feedback model predicts a circumferential pattern of fibers surrounding apical tissues and growing primordia, guided by the anisotropic curvature in such tissues. In contrast, during the initiation of tip growing root hairs, a star-like radial pattern has recently been observed. Here, we use detailed finite element models to analyze how a change in mechanical properties at the root hair initiation site can lead to star-like stress patterns in order to understand whether a stress-based feedback model can also explain the microtubule patterns seen during root hair initiation. We show that two independent mechanisms, individually or combined, can be sufficient to generate radial patterns. In the first, new material is added locally at the position of the root hair. In the second, increased tension in the initiation area provides a mechanism. Finally, we describe how a molecular model of Rho-of-plant (ROP) GTPases activation driven by auxin can position a patch of activated ROP protein basally along a 2D root epidermal cell plasma membrane, paving the way for models where mechanical and molecular mechanisms cooperate in the initial placement and outgrowth of root hairs.
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http://dx.doi.org/10.3389/fpls.2016.01560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5083785PMC
October 2016

Auxin Acts through MONOPTEROS to Regulate Plant Cell Polarity and Pattern Phyllotaxis.

Curr Biol 2016 12 3;26(23):3202-3208. Epub 2016 Nov 3.

European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany; Biological Sciences, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address:

The periodic formation of plant organs such as leaves and flowers gives rise to intricate patterns that have fascinated biologists and mathematicians alike for hundreds of years [1]. The plant hormone auxin plays a central role in establishing these patterns by promoting organ formation at sites where it accumulates due to its polar, cell-to-cell transport [2-6]. Although experimental evidence as well as modeling suggest that feedback from auxin to its transport direction may help specify phyllotactic patterns [7-12], the nature of this feedback remains unclear [13]. Here we reveal that polarization of the auxin efflux carrier PIN-FORMED 1 (PIN1) is regulated by the auxin response transcription factor MONOPTEROS (MP) [14]. We find that in the shoot, cell polarity patterns follow MP expression, which in turn follows auxin distribution patterns. By perturbing MP activity both globally and locally, we show that localized MP activity is necessary for the generation of polarity convergence patterns and that localized MP expression is sufficient to instruct PIN1 polarity directions non-cell autonomously, toward MP-expressing cells. By expressing MP in the epidermis of mp mutants, we further show that although MP activity in a single-cell layer is sufficient to promote polarity convergence patterns, MP in sub-epidermal tissues helps anchor these polarity patterns to the underlying cells. Overall, our findings reveal a patterning module in plants that determines organ position by orienting transport of the hormone auxin toward cells with high levels of MP-mediated auxin signaling. We propose that this feedback process acts broadly to generate periodic plant architectures.
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http://dx.doi.org/10.1016/j.cub.2016.09.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154752PMC
December 2016

Signaling from maize organ primordia via FASCIATED EAR3 regulates stem cell proliferation and yield traits.

Nat Genet 2016 07 16;48(7):785-91. Epub 2016 May 16.

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, New York, USA.

Shoot apical meristems are stem cell niches that balance proliferation with the incorporation of daughter cells into organ primordia. This balance is maintained by CLAVATA-WUSCHEL feedback signaling between the stem cells at the tip of the meristem and the underlying organizing center. Signals that provide feedback from organ primordia to control the stem cell niche in plants have also been hypothesized, but their identities are unknown. Here we report FASCIATED EAR3 (FEA3), a leucine-rich-repeat receptor that functions in stem cell control and responds to a CLAVATA3/ESR-related (CLE) peptide expressed in organ primordia. We modeled our results to propose a regulatory system that transmits signals from differentiating cells in organ primordia back to the stem cell niche and that appears to function broadly in the plant kingdom. Furthermore, we demonstrate an application of this new signaling feedback, by showing that weak alleles of fea3 enhance hybrid maize yield traits.
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http://dx.doi.org/10.1038/ng.3567DOI Listing
July 2016

An epidermis-driven mechanism positions and scales stem cell niches in plants.

Sci Adv 2016 Jan 29;2(1):e1500989. Epub 2016 Jan 29.

Sainsbury Laboratory, University of Cambridge, Bateman Street, Cambridge CB2 1LR, UK.; Computational Biology and Biological Physics Group, Department of Astronomy and Theoretical Physics, Lund University, S-221 00 Lund, Sweden.

How molecular patterning scales to organ size is highly debated in developmental biology. We explore this question for the characteristic gene expression domains of the plant stem cell niche residing in the shoot apical meristem. We show that a combination of signals originating from the epidermal cell layer can correctly pattern the key gene expression domains and notably leads to adaptive scaling of these domains to the size of the tissue. Using live imaging, we experimentally confirm this prediction. The identified mechanism is also sufficient to explain de novo stem cell niches in emerging flowers. Our findings suggest that the deformation of the tissue transposes meristem geometry into an instructive scaling and positional input for the apical plant stem cell niche.
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http://dx.doi.org/10.1126/sciadv.1500989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846443PMC
January 2016

Shifting foundations: the mechanical cell wall and development.

Curr Opin Plant Biol 2016 Feb 19;29:115-20. Epub 2016 Jan 19.

The Sainsbury Laboratory, University of Cambridge, Bateman Street, Cambridge CB2 1LR, UK; Computational Biology and Biological Physics Group, Department of Astronomy and Theoretical Physics, Lund University, Sölvegatan 14A, SE-223 62 Lund, Sweden.

The cell wall has long been acknowledged as an important physical mediator of growth in plants. Recent experimental and modelling work has brought the importance of cell wall mechanics into the forefront again. These data have challenged existing dogmas that relate cell wall structure to cell/organ growth, that uncouple elasticity from extensibility, and those which treat the cell wall as a passive and non-stressed material. Within this review we describe experiments and models which have changed the ways in which we view the mechanical cell wall, leading to new hypotheses and research avenues. It has become increasingly apparent that while we often wish to simplify our systems, we now require more complex multi-scale experiments and models in order to gain further insight into growth mechanics. We are currently experiencing an exciting and challenging shift in the foundations of our understanding of cell wall mechanics in growth and development.
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http://dx.doi.org/10.1016/j.pbi.2015.12.009DOI Listing
February 2016

Subcellular and supracellular mechanical stress prescribes cytoskeleton behavior in Arabidopsis cotyledon pavement cells.

Elife 2014 Apr 16;3:e01967. Epub 2014 Apr 16.

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.

Although it is a central question in biology, how cell shape controls intracellular dynamics largely remains an open question. Here, we show that the shape of Arabidopsis pavement cells creates a stress pattern that controls microtubule orientation, which then guides cell wall reinforcement. Live-imaging, combined with modeling of cell mechanics, shows that microtubules align along the maximal tensile stress direction within the cells, and atomic force microscopy demonstrates that this leads to reinforcement of the cell wall parallel to the microtubules. This feedback loop is regulated: cell-shape derived stresses could be overridden by imposed tissue level stresses, showing how competition between subcellular and supracellular cues control microtubule behavior. Furthermore, at the microtubule level, we identified an amplification mechanism in which mechanical stress promotes the microtubule response to stress by increasing severing activity. These multiscale feedbacks likely contribute to the robustness of microtubule behavior in plant epidermis. DOI: http://dx.doi.org/10.7554/eLife.01967.001.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3985187PMC
http://dx.doi.org/10.7554/eLife.01967DOI Listing
April 2014

Stress and strain provide positional and directional cues in development.

PLoS Comput Biol 2014 Jan 9;10(1):e1003410. Epub 2014 Jan 9.

Computational Biology & Biological Physics, Lund University, Lund, Sweden ; Sainsbury Laboratory, Cambridge University, Cambridge, United Kingdom.

The morphogenesis of organs necessarily involves mechanical interactions and changes in mechanical properties of a tissue. A long standing question is how such changes are directed on a cellular scale while being coordinated at a tissular scale. Growing evidence suggests that mechanical cues are participating in the control of growth and morphogenesis during development. We introduce a mechanical model that represents the deposition of cellulose fibers in primary plant walls. In the model both the degree of material anisotropy and the anisotropy direction are regulated by stress anisotropy. We show that the finite element shell model and the simpler triangular biquadratic springs approach provide equally adequate descriptions of cell mechanics in tissue pressure simulations of the epidermis. In a growing organ, where circumferentially organized fibers act as a main controller of longitudinal growth, we show that the fiber direction can be correlated with both the maximal stress direction and the direction orthogonal to the maximal strain direction. However, when dynamic updates of the fiber direction are introduced, the mechanical stress provides a robust directional cue for the circumferential organization of the fibers, whereas the orthogonal to maximal strain model leads to an unstable situation where the fibers reorient longitudinally. Our investigation of the more complex shape and growth patterns in the shoot apical meristem where new organs are initiated shows that a stress based feedback on fiber directions is capable of reproducing the main features of in vivo cellulose fiber directions, deformations and material properties in different regions of the shoot. In particular, we show that this purely mechanical model can create radially distinct regions such that cells expand slowly and isotropically in the central zone while cells at the periphery expand more quickly and in the radial direction, which is a well established growth pattern in the meristem.
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http://dx.doi.org/10.1371/journal.pcbi.1003410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886884PMC
January 2014

The MOSS Physcomitrella patens reproductive organ development is highly organized, affected by the two SHI/STY genes and by the level of active auxin in the SHI/STY expression domain.

Plant Physiol 2013 Jul;162(3):1406-19

Department of Plant Biology and Forest Genetics, Uppsala BioCenter, Swedish University of Agricultural Sciences and Linnéan Centre for Plant Biology, SE–750 07 Uppsala, Sweden.

In order to establish a reference for analysis of the function of auxin and the auxin biosynthesis regulators SHORT INTERNODE/STYLISH (SHI/STY) during Physcomitrella patens reproductive development, we have described male (antheridial) and female(archegonial) development in detail, including temporal and positional information of organ initiation. This has allowed us to define discrete stages of organ morphogenesis and to show that reproductive organ development in P. patens is highly organized and that organ phyllotaxis differs between vegetative and reproductive development. Using the PpSHI1 and PpSHI2 reporter and knockout lines, the auxin reporters GmGH3(pro):GUS and PpPINA(pro):GFP-GUS, and the auxin-conjugating transgene PpSHI2(pro):IAAL, we could show that the PpSHI genes, and by inference also auxin, play important roles for reproductive organ development in moss. The PpSHI genes are required for the apical opening of the reproductive organs, the final differentiation of the egg cell, and the progression of canal cells into a cell death program. The apical cells of the archegonium, the canal cells, and the egg cell are also sites of auxin responsiveness and are affected by reduced levels of active auxin, suggesting that auxin mediates PpSHI function in the reproductive organs.
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http://dx.doi.org/10.1104/pp.113.214023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707547PMC
July 2013