Visualizing the metazoan proliferation-quiescence decision in vivo

Cell proliferation and quiescence are intimately coordinated during metazoan development. Here, we adapt a cyclin-dependent kinase (CDK) sensor to uncouple these key events of the cell cycle in Caenorhabditis elegans and zebrafish through live-cell imaging. The CDK sensor consists of a fluorescently tagged CDK substrate that steadily translocates from the nucleus to the cytoplasm in response to increasing CDK activity and consequent sensor phosphorylation. We show that the CDK sensor can distinguish cycling cells in G1 from quiescent cells in G0, revealing a possible commitment point and a cryptic stochasticity in an otherwise invariant C. elegans cell lineage. Finally, we derive a predictive model of future proliferation behavior in C. elegans based on a snapshot of CDK activity in newly born cells. Thus, we introduce a live-cell imaging tool to facilitate in vivo studies of cell-cycle control in a wide-range of developmental contexts. </div

A developmental model for branching morphogenesis of lake cress compound leaf

Lake cress, Rorippa aquatica (Brassicaceae), is a semi-aquatic plant that exhibits a variety of leaf shapes, from simple leaves to highly branched compound leaves, depending on the environment. Leaf shape can vary within a single plant, suggesting that the variation can be explained by a simple model. In order to simulate the branched structure in the compound leaves of R. aquatica, we implemented reaction-diffusion (RD) patterning onto a theoretical framework that had been developed for serration distribution in the leaves of Arabidopsis thaliana, with the modification of the one-dimensional reaction-diffusion domain being deformed with the spatial periodicity of the RD pattern while expanding. This simple method using an iterative pattern could create regular and nested branching patterns. Subsequently, we verified the plausibility of our theoretical model by comparing it with the experimentally observed branching patterns. The results suggested that our model successfully predicted both the qualitative and quantitative aspects of the timing and positioning of branching in growing R. aquatica leaves

Investigation of institutional changes in the UK housing market using structural break tests and time-varying parameter models

This paper investigates the effects of institutional changes within the UK housing market in recent decades using structural break tests and time-varying parameter models. This approach is motivated by models of institutional change drawn from the political science literature which focus on the existence of both fast-moving and slow-moving institutional changes and the interactions between them as drivers of the dynamics of asset prices. As a methodological contribution, we use several time-varying parameter models for the first time in investigations of institutional change. Our findings support the existence of both structural breaks and continuous variance in parameters. This contributes to our understanding of the housing market in two respects. Firstly, the dates of structural breaks appear to better match unexpected market shocks rather than remarkable political events, and this supports prior institutional theory. Secondly, assessment of the effect of slow-moving institutional changes shows that people’s biased expectations rather than the economic fundamentals have increasingly played an important role in driving housing prices in the short run although fundamentals continue to drive house prices to converge to their long-run equilibrium

Stochastic loss and gain of symmetric divisions in the C. elegans epidermis perturbs robustness of stem cell number

Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes. Here, we start addressing these questions using the robust number of Caenorhabditis elegans epidermal stem cells, known as seam cells, as a readout. We employ genetics, cell lineage tracing, and single molecule imaging to show that mutations in lin-22, a Hes-related basic helix-loop-helix (bHLH) transcription factor, increase seam cell number variability. We show that the increase in phenotypic variability is due to stochastic conversion of normally symmetric cell divisions to asymmetric and vice versa during development, which affect the terminal seam cell number in opposing directions. We demonstrate that LIN-22 acts within the epidermal gene network to antagonise the Wnt signalling pathway. However, lin-22 mutants exhibit cell-to-cell variability in Wnt pathway activation, which correlates with and may drive phenotypic variability. Our study demonstrates the feasibility to study phenotypic trait variance in tractable model organisms using unbiased mutagenesis screens