Unite du Prof. Oates

Laboratoire

Publications associées (98)

Reaction wavefront theory of notochord segment patterning

Andrew Charles Oates

The vertebrate axis is segmented into repetitive structures, the vertebrae. In fish, these segmented structures are thought to form from the paraxial mesoderm and the adjacent notochord. Recent work revealed an autonomous patterning mechanism in the zebrafish notochord, with inputs from the segmented paraxial mesoderm. The notochord pattern is established in a sequential manner, progressing from anterior to posterior. Building on this previous work, here, we propose a reaction wavefront theory describing notochord patterning in zebrafish. The pattern is generated by an activator-inhibitor reaction-diffusion mechanism. Cues from the paraxial mesoderm are introduced as a profile of inhibitor sinks. Reactions are turned on by a wavefront that advances from anterior to posterior. We show that this reaction wavefront ensures that a pattern is formed sequentially, in register with the cues, despite the presence of fluctuations. We find that the velocity and shape of the reaction wavefront can modulate the prevalence of defective patterns. Normal patterning is supported in a wide range of sink profile wavelengths, while a minimum sink strength is required for the pattern to follow the cues. The theory predicts that distinct defect types occur for small or large wavelengths. Thus, the reaction wavefront theory provides a possible scenario for notochord patterning, with testable predictions that prompt future experiments.

FRONTIERS MEDIA SA2022

Chargement

Hunting for the wavefront: investigation of somite boundary positioning in zebrafish

Arianne Bercowsky Rama

Somitogenesis is the rhythmic and sequential formation of somites, which are tissue blocks that give rise to segmented adult body structures including the vertebrae and associated muscle. Somite formation is controlled by the segmentation clock, a population of genetic oscillators that are coordinated by an interplay of cell-intrinsic and -extrinsic spatiotemporal information. Disruption of the segmentation clock can lead to misplaced or defective somite boundaries, and consequently results in deformed adult structures (e.g., congenital scoliosis). Despite decades of research into how the segmentation clock pattern is established, and how it acts to position somite boundaries within the pre-segmental mesoderm(PSM), many open questions remain. The position where the somite boundary is set along the anteroposterior axis of the PSM has been named the "determination front". Question still remain as to the mechanism and location of the determination front, and what spatiotemporal information is instructive.Here I present three studies that tackle this question by advancing imaging and analysis tools such that questions that have persisted for decades can be directly addressed. My work contributed significantly to obtaining a better picture of how somite boundaries are precisely formed.

EPFL2022

Chargement

Multiscale light-sheet organoid imaging framework

Andrea Boni, Raphaël Ortiz, Petr Strnad

Live imaging of organoid growth remains a challenge: it requires long-term imaging of several samples simultaneously and dedicated analysis pipelines. Here the authors report an experimental and image processing framework to turn long-term light-sheet imaging of intestinal organoids into digital organoids. Organoids provide an accessible in vitro system to mimic the dynamics of tissue regeneration and development. However, long-term live-imaging of organoids remains challenging. Here we present an experimental and image-processing framework capable of turning long-term light-sheet imaging of intestinal organoids into digital organoids. The framework combines specific imaging optimization combined with data processing via deep learning techniques to segment single organoids, their lumen, cells and nuclei in 3D over long periods of time. By linking lineage trees with corresponding 3D segmentation meshes for each organoid, the extracted information is visualized using a web-based "Digital Organoid Viewer" tool allowing combined understanding of the multivariate and multiscale data. We also show backtracking of cells of interest, providing detailed information about their history within entire organoid contexts. Furthermore, we show cytokinesis failure of regenerative cells and that these cells never reside in the intestinal crypt, hinting at a tissue scale control on cellular fidelity.

NATURE PORTFOLIO2022

Chargement

A billion-year trend of amino acid substitutions in the mitochondrial genome

Jacques Fellay, Konstantin Popadin, Valeriia Timonina

SPRINGERNATURE2022

Chargement

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The opportunistic pathogen Pseudomonas aeruginosa explores surfaces using twitching motility powered by retractile extracellu-lar filaments called type IV pili (T4P). Single cells twitch by sequen-tial T4P extension, attachment, and retraction. How single cells coordinate T4P to efficiently navigate surfaces remains unclear. We demonstrate that P. aeruginosa actively directs twitching in the direction of mechanical input from T4P in a process called mechanotaxis. The Chp chemotaxis-like system controls the bal-ance of forward and reverse twitching migration of single cells in response to the mechanical signal. Collisions between twitching cells stimulate reversals, but Chp mutants either always or never reverse. As a result, while wild-type cells colonize surfaces uni-formly, collision-blind Chp mutants jam, demonstrating a function for mechanosensing in regulating group behavior. On surfaces, Chp senses T4P attachment at one pole, thereby sensing a spatially resolved signal. As a result, the Chp response regulators PilG and PilH control the polarization of the extension motor PilB. PilG stim-ulates polarization favoring forward migration, while PilH inhibits polarization, inducing reversal. Subcellular segregation of PilG and PilH efficiently orchestrates their antagonistic functions, ultimately enabling rapid reversals upon perturbations. The distinct localiza-tion of response regulators establishes a signaling landscape known as local excitation-global inhibition in higher-order organ-isms, identifying a conserved strategy to transduce spatially resolved signals.

NATL ACAD SCIENCES2021

Chargement

Temperature is one of the most important range-limiting factors for many seaweeds. Driven by the recent climatic changes, rapid northward shifts of species' distribution ranges can potentially modify the phylogeographic signature of Last Glacial Maximum. We explored this question in detail in the cold-tolerant kelp species Saccharina latissima, using microsatellites and double digest restriction site-associated DNA sequencing ( ddRAD-seq) derived single nucleotide polymorphisms (SNPs) to analyze the genetic diversity and structure in 11 sites spanning the entire European Atlantic latitudinal range of this species. In addition, we checked for statistical correlation between genetic marker allele frequencies and three environmental proxies (sea surface temperature, salinity, and water turbidity). Our findings revealed that genetic diversity was significantly higher for the northernmost locality (Spitsbergen) compared to the southern ones (Northern Iberia), which we discuss in light of the current state of knowledge on phylogeography of S. latissima and the potential influence of the recent climatic changes on the population structure of this species. Seven SNPs and 12 microsatellite alleles were found to be significantly associated with at least one of the three environmental variables. We speculate on the putative adaptive functions of the genes associated with the outlier markers and the importance of these markers for successful conservation and aquaculture strategies for S. latissima in this age of rapid global change.

MDPI2020

Chargement

Integrity of rhythmic spatial gene expression patterns in the vertebrate segmentation clock requires local synchronization between neighboring cells by Delta-Notch signaling and its inhibition causes defective segment boundaries. Whether deformation of the oscillating tissue complements local synchronization during patterning and segment formation is not understood. We combine theory and experiment to investigate this question in the zebrafish segmentation clock. We remove a Notch inhibitor, allowing resynchronization, and analyze embryonic segment recovery. We observe unexpected intermingling of normal and defective segments, and capture this with a new model combining coupled oscillators and tissue mechanics. Intermingled segments are explained in the theory by advection of persistent phase vortices of oscillators. Experimentally observed changes in recovery patterns are predicted in the theory by temporal changes in tissue length and cell advection pattern. Thus, segmental pattern recovery occurs at two length and time scales: rapid local synchronization between neighboring cells, and the slower transport of the resulting patterns across the tissue through morphogenesis.

ELIFE SCIENCES PUBLICATIONS LTD2021

Chargement

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Video Abstract Video Abstract: Theory of time delayed genetic oscillations with external noisy regulation We present a general theory of noisy genetic oscillators with externally regulated production rate and multiplicative noise. The observables that characterize the genetic oscillator are discussed, and it is shown how their statistics depend on the externally regulated production rate. We show that these observables have generic features that are observed in two different experimental systems: the expression of the circadian clock genes in fibroblasts, and in the transient and oscillatory dynamics of the segmentation clock genes observed in cells disassociated from zebrafish embryos. Our work shows that genetic oscillations with diverse biological contexts can be understood in a common framework based on a delayed negative feedback system, and regulator dynamics.

IOP PUBLISHING LTD2021

Chargement

Capturing Cardiogenesis in Gastruloids

Andrea Boni, Nicolas Antoine Vincent Broguiere, Mehmet Ugur Girgin, Romain Guiet, Matthias Lütolf, Giuliana Rossi

Organoids are powerful models for studying tissue development, physiology, and disease. However, current culture systems disrupt the inductive tissue-tissue interactions needed for the complex morphogenetic processes of native organogenesis. Here, we show that mouse embryonic stem cells (mESCs) can be coaxed to robustly undergo fundamental steps of early heart organogenesis with an in-vivo-like spatiotemporal fidelity. These axially patterned embryonic organoids (gastruloids) mimic embryonic development and support the generation of cardiovascular progenitors, including first and second heart fields. The cardiac progenitors self-organize into an anterior domain reminiscent of a cardiac crescent before forming a beating cardiac tissue near a putative primitive gut-like tube, from which it is separated by an endocardial-like layer. These findings unveil the surprising morphogenetic potential of mESCs to execute key aspects of organogenesis through the coordinated development of multiple tissues. This platform could be an excellent tool for studying heart development in unprecedented detail and throughput.

CELL PRESS2021

Chargement

Living cells adjust their sensing and migratory machinery in response to changes in their environment. In this work, we show that cells of the social amoeba Dictyostelium discoideum modulate the dynamical state of their actin cytoskeleton in response to an external pulse of the chemoattractant cyclic adenosine monophosphate (cAMP). In particular, we focus on a population of cells that exhibits noisy oscillatory cycles of actin polymerization and systematically study receptor-induced transitions in their cytoskeletal dynamics. In response to a short external pulse of cAMP, these cells adopt a noisy quiescent state, before returning to their initial, oscillatory dynamics. The response exhibits a biphasic time profile, with a duration that shows strong variability between cells; it can extend as long as approximately twelve oscillation cycles. We propose a model that is based on a generic nonlinear noisy oscillator. Our theoretical analysis suggests that the transient termination of oscillations in response to a receptor stimulus occurs via a Hopf bifurcation.

AMER PHYSICAL SOC2020

Chargement