Publications

Mawsoniidae is a family of coelacanths restricted to the Mesozoic. During the Cretaceous, mawsoniids were mainly represented by the Mawsonia/Axelrodichthy complex, long known to be from western Gondwana only (South America and Africa). This apparent biogeographical distribution then faded following the discovery of representatives in the Late Cretaceous of Laurasia (Europe and North America). We report here the presence, in the Lower Cretaceous site of Kham Phok, NE Thailand, of an angular bone referred to the Mawsonia/Axelrodichthys complex. A comparison with angulars referring to both genera found in various regions of the world between the Late Jurassic and the Late Cretaceous indicated that the distinctions between these genera, and even more so between their constituent species, are unclear. This discovery is further confirmation of the very slow morphological evolution within this lineage, which may explain why their evolutionary history appears to be disconnected, at least in part, from their geographical distribution over time.

The analysis of ancient mitochondrial DNA from osteological remains has challenged previous conclusions drawn from the analysis of mitochondrial DNA from present populations, notably by revealing an absence of genetic continuity between the Neolithic and modern populations in Central Europe. Our study investigates how to reconcile these contradictions at the mitochondrial level using a modeling approach.

Age profiling of archaeological bone assemblages can inform on past animal management practices, but is limited by the fragmentary nature of the fossil record and the lack of universal skeletal markers for age. DNA methylation clocks offer new, albeit challenging, alternatives for estimating the age-at-death of ancient individuals. Here, we take advantage of the availability of a DNA methylation clock based on 31,836 CpG sites and dental age markers in horses to assess age predictions in 84 ancient remains. We evaluate our approach using whole-genome sequencing data and develop a capture assay providing reliable estimates for only a fraction of the cost. We also leverage DNA methylation patterns to assess castration practice in the past. Our work opens for a deeper characterization of past husbandry and ritual practices and holds the potential to reveal age mortality profiles in ancient societies, once extended to human remains.

Shape transformations of epithelial tissues in three dimensions, which are crucial for embryonic development or in vitro organoid growth, can result from active forces generated within the cytoskeleton of the epithelial cells. How the interplay of local differential tensions with tissue geometry and with external forces results in tissue-scale morphogenesis remains an open question. Here, we describe epithelial sheets as active viscoelastic surfaces and study their deformation under patterned internal tensions and bending moments. In addition to isotropic effects, we take into account nematic alignment in the plane of the tissue, which gives rise to shape-dependent, anisotropic active tensions and bending moments. We present phase diagrams of the mechanical equilibrium shapes of pre-patterned closed shells and explore their dynamical deformations. Our results show that a combination of nematic alignment and gradients in internal tensions and bending moments is sufficient to reproduce basic building blocks of epithelial morphogenesis, including fold formation, budding, neck formation, flattening, and tubulation.

The molecular mechanisms that maintain cellular identities and prevent dedifferentiation or transdifferentiation remain mysterious. However, both processes are transiently used during animal regeneration. Therefore, organisms that regenerate their organs, appendages, or even their whole body offer a fruitful paradigm to investigate the regulation of cell fate stability. Here, we used as a model system and show that Zic4, whose expression is controlled by Wnt3/β-catenin signaling and the Sp5 transcription factor, plays a key role in tentacle formation and tentacle maintenance. Reducing expression suffices to induce transdifferentiation of tentacle epithelial cells into foot epithelial cells. This switch requires the reentry of tentacle battery cells into the cell cycle without cell division and is accompanied by degeneration of nematocytes embedded in these cells. These results indicate that maintenance of cell fate by a Wnt-controlled mechanism is a key process both during homeostasis and during regeneration.

The vertebrate body displays a segmental organization which is most conspicuous in the periodic organization of the vertebral column and peripheral nerves. This metameric organization is first implemented when somites, which contain the precursors of skeletal muscles and vertebrae, are rhythmically generated from the presomitic mesoderm (PSM). Somites then become subdivided into anterior and posterior compartments essential for vertebral formation and segmental patterning of the peripheral nervous system. How this key somitic subdivision is established remains poorly understood. Here we introduce novel tridimensional culture systems of human pluripotent stem cells (PSCs), called Somitoids and Segmentoids, which recapitulate the formation of somite-like structures with antero-posterior (AP) identity. We identify a key function of the segmentation clock in converting temporal rhythmicity into the spatial regularity of anterior and posterior somitic compartments. We show that an initial salt-and-pepper expression of the segmentation gene MESP2 in the newly formed segment is transformed into compartments of anterior and posterior identity via an active cell sorting mechanism. Our work demonstrates that the major patterning modules involved in somitogenesis including the clock and wavefront, AP polarity patterning and somite epithelialization can be dissociated and operate independently in our in vitro systems. Together we define a novel framework for the symmetry breaking process initiating somite polarity patterning. Our work provides a valuable platform to decode general principles of somitogenesis and advance knowledge of human development.

We introduce a modelling and simulation framework for cell aggregates in three dimensions based on interacting active surfaces. Cell mechanics is captured by a physical description of the acto-myosin cortex that includes cortical flows, viscous forces, active tensions, and bending moments. Cells interact with each other via short-range forces capturing the effect of adhesion molecules. We discretise the model equations using a finite element method, and provide a parallel implementation in C++. We discuss examples of application of this framework to small and medium-sized aggregates: we consider the shape and dynamics of a cell doublet, a planar cell sheet, and a growing cell aggregate. This framework opens the door to the systematic exploration of the cell to tissue-scale mechanics of cell aggregates, which plays a key role in the morphogenesis of embryos and organoids.

Variation in genes involved in the absorption, distribution, metabolism, and excretion of drugs (ADME) can influence individual response to therapeutic treatment. Study of ADME genetic diversity in human populations has led to evolutionary hypotheses of adaptation to distinct chemical environments. Population differentiation in measured drug metabolism phenotypes is however scarcely documented, often indirectly estimated via genotype-predicted phenotypes. We administered seven probe compounds devised to target six cytochrome P450 enzymes and the P-glycoprotein activity to assess phenotypic variation in four populations along a latitudinal transect spanning over Africa, the Middle East and Europe (349 healthy Ethiopian, Omani, Greek and Czech volunteers). We demonstrate significant population differentiation for all phenotypes except the one measuring CYP2D6 activity. GWAS evidenced that the variability of phenotypes measuring CYP2B6, CYP2C9, CYP2C19 and CYP2D6 activity was associated with genetic variants linked to the corresponding encoding genes, and to additional genes for the latter three. Instead, GWAS did not indicate any association between genetic diversity and the phenotypes measuring CYP1A2, CYP3A4 and P-glycoprotein activity. Genome scans of selection highlighted multiple candidate regions, a few of which included ADME genes, but none overlapped with the GWAS candidates. Our results suggest that different mechanisms have been shaping the evolution of these phenotypes, including phenotypic plasticity, and possibly some form of balancing selection. We discuss how these contrasted results highlight diverse evolutionary trajectories of ADME genes and proteins, consistent with the wide spectrum of both endogenous and exogenous molecules that are their substrates.

Rodents perceive pheromones via vomeronasal receptors encoded by highly evolutionarily dynamic Vr and Fpr gene superfamilies. We report here that high numbers of V1r pseudogenes are scattered in mammalian genomes, contrasting with the clustered organization of functional V1r and Fpr genes. We also found that V1r pseudogenes are more likely to be expressed when located in a functional V1r gene cluster than when isolated. To explore the potential regulatory role played by the association of functional vomeronasal receptor genes with their clusters, we dissociated the mouse from its native cluster via transgenesis. Singular and specific transgenic transcription was observed in young vomeronasal neurons but was only transient. Our study of natural and artificial dispersed gene duplications uncovers the existence of transcription-stabilizing elements not coupled to vomeronasal gene units but rather associated with vomeronasal gene clusters and thus explains the evolutionary conserved clustered organization of functional vomeronasal genes.

Skin color patterning in vertebrates emerges at the macroscale from microscopic cell-cell interactions among chromatophores. Taking advantage of the convergent scale-by-scale skin color patterning dynamics in five divergent species of lizards, we quantify the respective efficiencies of stochastic (Lenz-Ising and cellular automata, sCA) and deterministic reaction-diffusion (RD) models to predict individual patterns and their statistical attributes. First, we show that all models capture the underlying microscopic system well enough to predict, with similar efficiencies, neighborhood statistics of adult patterns. Second, we show that RD robustly generates, in all species, a substantial gain in scale-by-scale predictability of individual adult patterns without the need to parametrize the system down to its many cellular and molecular variables. Third, using 3D numerical simulations and Lyapunov spectrum analyses, we quantitatively demonstrate that, given the non-linearity of the dynamical system, uncertainties in color measurements at the juvenile stage and in skin geometry variation explain most, if not all, of the residual unpredictability of adult individual scale-by-scale patterns. We suggest that the efficiency of RD is due to its intrinsic ability to exploit mesoscopic information such as continuous scale colors and the relations among growth, scales geometries, and the pattern length scale. Our results indicate that convergent evolution of CA patterning dynamics, leading to dissimilar macroscopic patterns in different species, is facilitated by their spontaneous emergence under a large range of RD parameters, as long as a Turing instability occurs in a skin domain with periodic thickness. VIDEO ABSTRACT.