Publications

Proper orientation of the mitotic spindle plays a crucial role in embryos, during tissue development, and in adults, where it functions to dissipate mechanical stress to maintain tissue integrity and homeostasis. While mitotic spindles have been shown to reorient in response to external mechanical stresses, the subcellular cues that mediate spindle reorientation remain unclear. Here, we used a combination of optogenetics and computational modeling to investigate how mitotic spindles respond to inhomogeneous tension within the actomyosin cortex. Strikingly, we found that the optogenetic activation of RhoA only influences spindle orientation when it is induced at both poles of the cell. Under these conditions, the sudden local increase in cortical tension induced by RhoA activation reduces pulling forces exerted by cortical regulators on astral microtubules. This leads to a perturbation of the balance of torques exerted on the spindle, which causes it to rotate. Thus, spindle rotation in response to mechanical stress is an emergent phenomenon arising from the interaction between the spindle positioning machinery and the cell cortex.

The expression of some genes depends on large, adjacent regions of the genome that contain multiple enhancers. These regulatory landscapes frequently align with Topologically Associating Domains (TADs), where they integrate the function of multiple similar enhancers to produce a global, TAD-specific regulation. We asked if an individual enhancer could overcome the influence of one of these landscapes, to drive gene transcription. To test this, we transferred an enhancer from its native location, into a nearby TAD with a related yet different functional specificity. We used the biphasic regulation of Hoxd genes during limb development as a paradigm. These genes are first activated in proximal limb cells by enhancers located in one TAD, which is then silenced when the neighboring TAD activates its enhancers in distal limb cells. We transferred a distal limb enhancer into the proximal limb TAD and found that its new context suppresses its normal distal specificity, even though it is bound by HOX13 transcription factors, which are responsible for the distal activity. This activity can be rescued only when a large portion of the surrounding environment is removed. These results indicate that, at least in some cases, the functioning of enhancer elements is subordinated to the host chromatin context, which can exert a dominant control over its activity.

Rhinoviruses (RV) have been shown to inhibit subsequent infection by heterologous respiratory viruses, including influenza viruses and severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). To better understand the mechanisms whereby RV protects against pulmonary coronavirus infection, we used a native murine virus, mouse hepatitis virus strain 1 (MHV-1), that causes severe disease in the lungs of infected mice. We found that priming of the respiratory tract with RV completely prevented mortality and reduced morbidity of a lethal MHV-1 infection. Replication of MHV-1 was reduced in RV-primed mouse lungs although expression of antiviral type I interferon, IFN-β, was more robust in mice infected with MHV-1 alone. We further showed that signaling through the type I interferon receptor was required for survival of mice given a non-lethal dose of MHV-1. RV-primed mice had reduced pulmonary inflammation and hemorrhage and influx of leukocytes, especially neutrophils, in the airways upon MHV-1 infection. Although MHV-1 replication was reduced in RV-primed mice, RV did not inhibit MHV-1 replication in coinfected lung epithelial cells . In summary, RV-mediated priming in the respiratory tract reduces viral replication, inflammation, and tissue damage, and prevents mortality of a pulmonary coronavirus infection in mice. These results contribute to our understanding of how distinct respiratory viruses interact with the host to affect disease pathogenesis, which is a critical step in understanding how respiratory viral coinfections impact human health.

In mammals, chemoperception relies on a diverse set of neuronal sensors able to detect chemicals present in the environment, and to adapt to various levels of stimulation. The contribution of endogenous and external factors to these neuronal identities remains to be determined. Taking advantage of the parallel coding lines present in the olfactory system, we explored the potential variations of neuronal identities before and after olfactory experience. We found that at rest, the transcriptomic profiles of mouse olfactory sensory neuron populations are already divergent, specific to the olfactory receptor they express, and are associated with the sequence of these latter. These divergent profiles further evolve in response to the environment, as odorant exposure leads to reprogramming via the modulation of transcription. These findings highlight a broad range of sensory neuron identities that are present at rest and that adapt to the experience of the individual, thus adding to the complexity and flexibility of sensory coding.

Darwin pointed out that “species of different genera and classes have not changed at the same rate” (Darwin, 1859, chapter X). Besides, he coined the expression “living fossils” for lineages whose “new forms will have been more slowly formed, and old forms more slowly exterminated” (chapter IV), among other characteristics. This expression has become popular, but has sometimes been misunderstood as meaning that some organisms do not evolve. It has also been commonly used by paleontologists and evolutionary biologists to describe a general pattern of relative stasis in morphological evolution in some lineages. Darwin's definition of the concept was imprecise and he considered that “species and groups of species, which are called aberrant, and which may fancifully be called living fossils, will aid us in forming a picture of the ancient forms of life” (Darwin, 1859, Chapter XIV). For more than 200 years, nevertheless, debates have raged on the definition of the concept (e.g., Bennett et al., 2017, 2018; Lidgard and Love, 2018; Turner, 2019), and more generally on the merits of its use in the life sciences (e.g., Casane and Laurenti, 2013; Naville et al., 2015). Although Darwin (1859) cited several taxa of fish as examples of “living fossils,” he did not mention the coelacanths, or actinistians, which were only known as fossils at his time. Huxley, however, soon after (1866) noticed the low anatomical disparity of coelacanths throughout their history. Since that time, and especially after the discovery of the living Latimeria in 1938 (Smith, 1939), the coelacanth has become an iconic symbol of the “living fossil” due to the slow morphological evolution illustrated by the fossil record of the clade, and its supposed affinities with tetrapods. Only the question of evolutionary rate is addressed here, not the question of ancestral status or other “living fossil” characteristics attributed to coelacanths. The low rate of evolution based on a lasting generalist morphological Bauplan has been confirmed by most subsequent authors who have worked on the group (Schaeffer, 1952; Cloutier, 1991; Forey, 1998; Schultze, 2004; Zhu et al., 2012; Cavin and Guinot, 2014), knowing that there are also exceptions to this general Bauplan (e.g., Friedman and Coates, 2006; Wendruff and Wilson, 2012; Cavin et al., 2017). However, part of the community of researchers working on fossil and living coelacanths avoids using this expression.

Entropy production plays a fundamental role in the study of nonequilibrium systems by offering a quantitative handle on the degree of time-reversal symmetry breaking. It depends crucially on the degree of freedom considered as well as on the scale of description. How the entropy production at one resolution of the degrees of freedom is related to the entropy production at another resolution is a fundamental question which has recently attracted interest. This relationship is of particular relevance to coarse-grained and continuum descriptions of a given phenomenon. In this work, we derive the scaling of the entropy production under iterative coarse graining on the basis of the correlations of the underlying microscopic transition rates for noninteracting particles in active disordered media. Our approach unveils a natural criterion to distinguish equilibrium-like and genuinely nonequilibrium macroscopic phenomena based on the sign of the scaling exponent of the entropy production per mesostate.

Over the past decade, the increasing wealth of new archaeological data on the Middle Stone Age (MSA) in Senegal and Mali has broadened our understanding of West Africa's contributions to cultural developments. Within the West African sequence, the phase of Marine Isotope Stage 3 (MIS 3, ca. 59-24 ka) yielded so far the best known and extensive archaeological information. The site of Toumboura III encompasses an occupation dated by optically stimulated luminescence (OSL) to between 40 ± 3 ka and 30 ± 3 ka. It provides the largest, well-dated, and stratified lithic assemblage in West Africa for the MSA and sheds light on an unprecedented cultural expression for this period, adding to the notable diversity of the late MSA in this region. We conducted a technological analysis of the lithic components following the approach. The lithic assemblage features a prevalence of bifacial technology and the exploitation of flakes as blanks for tool production. The craftspeople manufactured distinct types of bifacial tools, including small bifacial points shaped by pressure technique. The new data from Toumboura III demonstrate behavioral patterns that are entirely new in the region. By revealing behavioral innovations and technological particularities, these results on the techno-cultural dynamics during the MIS 3 phase of the MSA enhance our understanding of the complex Pleistocene population history in this part of Africa.

Generation of surrogate cells with stable functional identities is crucial for developing cell-based therapies. Efforts to produce insulin-secreting replacement cells to treat diabetes require reliable tools to assess islet cellular identity. Here, we conduct a thorough single-cell transcriptomics meta-analysis to identify robustly expressed markers used to build genesets describing the identity of human α-, β-, γ- and δ-cells. These genesets define islet cellular identities better than previously published genesets. We show their efficacy to outline cell identity changes and unravel some of their underlying genetic mechanisms, whether during embryonic pancreas development or in experimental setups aiming at developing glucose-responsive insulin-secreting cells, such as pluripotent stem-cell differentiation or in adult islet cell reprogramming protocols. These islet cell type-specific genesets represent valuable tools that accurately benchmark gain and loss in islet cell identity traits.

The global body-fossil record of marine 'fishes' from the time interval immediately preceding the Cretaceous-Paleogene Extinction is markedly poor. This deficiency appears to be further exacerbated with regards to offshore and deep-water taxa, obscuring our understanding of the state and composition of corresponding vertebrate faunas at the onset of this major extinction event. Recent fieldwork in the mid-late Maastrichtian exposures of the Pindos Unit in Gavdos Island, Greece, yielded a small but informative sample of fossil 'fishes', which inhabited the Tethys approximately three to four million years before the extinction. In this work we describe this sample, which comprises between eight and nine discrete morphotypes of various size classes, belonging to †Ichthyodectoidei, Aulopiformes (†Dercetidae, †Enchodontidae, †Ichthyotringidae), cf. †Sardinioididae, as well as the hexanchid shark †Gladioserratus sp. The new material expands the faunal list for the Maastrichtian of Gavdos Island, and the Pindos Unit as a whole, and further allows for the description of a new genus and species of †Enchodontidae and a new species of †Ichthyotringidae. The two new taxa are found to be widespread in the Maastrichtian of the Pindos Unit. The overall character of the assemblage agrees with previous interpretations of an offshore and rather deep depositional environment for the fossiliferous horizons. Furthermore, it exhibits a higher diversity than, and little taxonomic overlap with penecontemporaneous teleost assemblages from the Tethys, and informs on the otherwise poorly known Maastrichtian offshore and deep-water marine ichthyofaunas of the region.

Quaternary climatic oscillations had a large impact on European biogeography. Alternation of cold and warm stages caused recurrent glaciations, massive vegetation shifts, and large-scale range alterations in many species. The Eurasian steppe biome and its grasslands are a noteworthy example; they underwent climate-driven, large-scale contractions during warm stages and expansions during cold stages. Here, we evaluate the impact of these range alterations on the late Quaternary demography of several phylogenetically distant plant and insect species, typical of the Eurasian steppes. We compare three explicit demographic hypotheses by applying an approach combining convolutional neural networks with approximate Bayesian computation. We identified congruent demographic responses of cold stage expansion and warm stage contraction across all species, but also species-specific effects. The demographic history of the Eurasian steppe biota reflects major paleoecological turning points in the late Quaternary and emphasizes the role of climate as a driving force underlying patterns of genetic variance on the biome level.