Steroid hormone pulsing drives cyclic gene expression.

Transcriptional cycling of activated glucocorticoid receptor (GR) and ultradian glucocorticoid secretion are well established processes. Ultradian hormone release is now shown to result in pulsatile gene transcription through dynamic exchange of GR with the target-gene promoter and GR cycling through the chaperone machinery

Unveiling inter-embryo variability in spindle length over time: Towards quantitative phenotype analysis

International audienceHow can inter-individual variability be quantified? Measuring many features per experiment raises the question of choosing them to recapitulate high-dimensional data. Tackling this challenge on spindle elongation phenotypes, we showed that only three typical elongation patterns describe spindle elongation in C. elegans one-cell embryo. These archetypes, automatically extracted from the experimental data using principal component analysis (PCA), accounted for more than 95% of inter-individual variability of more than 1600 experiments across more than 100 different conditions. The two first archetypes were related to spindle average length and anaphasic elongation rate. The third archetype, accounting for 6% of the variability, was novel and corresponded to a transient spindle shortening in late metaphase, reminiscent of kinetochore function-defect phenotypes. Importantly, these three archetypes were robust to the choice of the dataset and were found even considering only non-treated conditions. Thus, the inter-individual differences between genetically perturbed embryos have the same underlying nature as natural inter-individual differences between wild-type embryos, independently of the temperatures. We thus propose that beyond the apparent complexity of the spindle, only three independent mechanisms account for spindle elongation, weighted differently in the various conditions. Interestingly, the spindle-length archetypes covered both metaphase and anaphase, suggesting that spindle elongation in late metaphase is sufficient to predict the late anaphase length. We validated this idea using a machine-learning approach. Finally, given amounts of these three archetypes could represent a quantitative phenotype. To take advantage of this, we set out to predict interacting genes from a seed based on the PCA coefficients. We exemplified this firstly on the role of tpxl-1 whose homolog tpx2 is involved in spindle microtubule branching, secondly the mechanism regulating metaphase length, and thirdly the central spindle players which set the length at anaphase. We found novel interactors not in public databases but supported by recent experimental publications

Only three principal components account for inter-embryo variability of the spindle length over time

Abstract How does inter-individual variability emerge? When measuring a large number of features per experiment/individual, this question becomes non-trivial. One challenge lies in choosing features to recapitulate high-dimension data. In this paper, we focus on spindle elongation phenotype to highlight how a data-driven approach can help. We showed that only three typical elongation patterns could describe spindle elongation in C. elegans one-cell embryo. We called them archetypes. These archetypes were automatically extracted from the experimental data using principal component analysis (PCA) rather than defined a priori. They accounted for more than 85% of inter-individual variability in a dataset of more than 1600 experiments across more than 100 different experimental conditions (RNAi, mutants, changes in temperature, etc.). The two first archetypes were consistent with standard measures in the field, namely the average spindle length and the spindle elongation rate both in late metaphase and anaphase. However, our archetypes were not strictly corresponding to these manually-set features. The third archetype, accounting for 6% of the variance, was novel and corresponded to a transient spindle shortening in late metaphase. We propose that it is part of spindle elongation dynamics in all conditions. It is reminiscent of the elongation pattern observed upon defects in kinetochore function. Notably, the same archetypes emerged when analysing non-treated embryos only at various temperatures. Interestingly, because these archetypes were not specific to metaphase or anaphase, it implied that spindle elongation around anaphase-onset is sufficient to predict its late anaphase length. We validated this idea using a machine-learning approach. Despite the apparent variability in phenotypes across the various conditions, inter-individual differences between embryos depleted from one cell division-related protein have the same underlying nature as inter-individual differences naturally arising between wild-type embryos. The same conclusion holds when analysing embryos dividing at various temperatures. We thus propose that beyond the apparent complexity of the spindle, only three independent mechanisms account for spindle elongation, and contribute differently in the various conditions, meanwhile, no mechanism is specific to any condition

A genetic Xenopus laevis tadpole model to study lymphangiogenesis

Lymph vessels control fluid homeostasis, immunity and metastasis. Unraveling the molecular basis of lymphangiogenesis has been hampered by the lack of a small animal model that can be genetically manipulated. Here, we show that Xenopus tadpoles develop lymph vessels from lymphangioblasts or, through transdifferentiation, from venous endothelial cells. Lymphangiography showed that these lymph vessels drain lymph, through the lymph heart, to the venous circulation. Morpholino-mediated knockdown of the lymphangiogenic factor Prox1 caused lymph vessel defects and lymphedema by impairing lymphatic commitment. Knockdown of vascular endothelial growth factor C (VEGF-C) also induced lymph vessel defects and lymphedema, but primarily by affecting migration of lymphatic endothelial cells. Knockdown of VEGF-C also resulted in aberrant blood vessel formation in tadpoles. This tadpole model offers opportunities for the discovery of new regulators of lymphangiogenesis.status: publishe

The Transcription Factor Encyclopedia

Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe .Medical Genetics, Department ofMedicine, Faculty ofMolecular Medicine and Therapeutics, Centre forScience, Faculty ofNon UBCReviewedFacult