Publications

In a recent article, Immel et al. (Immel A, Key FM, Szolek A, Barquera R, Robinson MK, Harrison GF, Palmer WH, Spyrou MA, Susat J, Krause-Kyora B, et al. 2021. Analysis of genomic DNA from medieval plague victims suggests long-term effect of Yersinia pestis on human immunity genes. Mol Biol Evol. 38:4059-4076) extracted DNA from 36 individuals dead from plague in Ellwangen, Southern Germany, during the 16th century. By comparing their human leukocyte antigen (HLA) genotypes with those of 50 present-day Ellwangen inhabitants, the authors reported a significant decrease of HLA-B*51:01 and HLA-C*06:02 and a significant increase of HLA-DRB1*13:01/13:02 frequencies from ancient to modern populations. After comparing these frequencies with a larger sample of 8,862 modern Germans and performing simulations of natural selection, they concluded that these changes had been driven by natural selection. In an attempt to provide more evidence on such stimulating results, we explored the HLA frequency patterns over all of Europe, we predicted binding affinities of HLA-B/C/DRB1 alleles to 106,515 Yersinia pestis-derived peptides, and we performed forward simulations of HLA genetic profiles under neutrality. Our analyses do not sustain the conclusions of HLA protection or susceptibility to plague based on ancient DNA.

In addition to its ability to regenerate any amputated body part, the Hydra freshwater polyp shows the amazing ability to regenerate as a full polyp after a complete dissociation of its tissues. The developmental processes at work in reaggregates undergoing whole-body regeneration can be investigated at the molecular level by RNA interference (RNAi). Here we provide a protocol that combines β-catenin RNAi with reaggregation. This protocol serves as a basis to generate "RNAi-reaggregates," followed by the extraction of high-quality RNA for the precise quantification of gene expression by real-time PCR. This protocol is efficient, providing both a molecular signature, with the significant downregulation of β-catenin and Wnt3, as well as a robust phenotype, the lack of axis formation, which is observed in all reaggregates.

The freshwater Hydra polyp is a versatile model to study whole-body regeneration from a developmental as well as a cellular point of view. The outstanding regenerative capacities of Hydra are based on its three populations of adult stem cells located in the central body column of the animal. There, these three populations, gastrodermal epithelial, epidermal epithelial, and interstitial, continuously cycle in homeostatic conditions, and their activity is locally regulated after mid-gastric bisection. Moreover, they present an unusual cycling behavior with a short G1 phase and a pausing in G2. This particular cell cycle has been studied for a long time with classical microscopic methods. We describe here two flow cytometry methods that provide accurate and reproducible quantitative data to monitor cell cycle regulation in homeostatic and regenerative contexts. We also present a cell sorting procedure based on flow cytometry, whereby stem cells expressing a fluorescent reporter protein in transgenic lines can be enriched for use in applications such as transcriptomic, proteomic, or cell cycle analysis.

As organs and tissues approach their normal size during development or regeneration, growth slows down, and cell proliferation progressively comes to a halt. Among the various processes suggested to contribute to growth termination, mechanical feedback, perhaps via adherens junctions, has been suggested to play a role. However, since adherens junctions are only present in a narrow plane of the subapical region, other structures are likely needed to sense mechanical stresses along the apical-basal (A-B) axis, especially in a thick pseudostratified epithelium. This could be achieved by nuclei, which have been implicated in mechanotransduction in tissue culture. In addition, mechanical constraints imposed by nuclear crowding and spatial confinement could affect interkinetic nuclear migration (IKNM), which allows G2 nuclei to reach the apical surface, where they normally undergo mitosis. To explore how mechanical constraints affect IKNM, we devised an individual-based model that treats nuclei as deformable objects constrained by the cell cortex and the presence of other nuclei. The model predicts changes in the proportion of cell-cycle phases during growth, which we validate with the cell-cycle phase reporter FUCCI (Fluorescent Ubiquitination-based Cell Cycle Indicator). However, this model does not preclude indefinite growth, leading us to postulate that nuclei must migrate basally to access a putative basal signal required for S phase entry. With this refinement, our updated model accounts for the observed progressive slowing down of growth and explains how pseudostratified epithelia reach a stereotypical thickness upon completion of growth.

The rapid development of ancient DNA (aDNA) analysis in the last decades has induced a paradigm shift in ecology and evolution. Driven by a combination of breakthroughs in DNA isolation techniques, high-throughput sequencing and bioinformatics, ancient genome-scale data for a rapidly growing variety of taxa is now available, allowing researchers to directly observe demographic and evolutionary processes over time. However, the vast majority of palaeogenomic studies still focuses on human or animal remains. In this article, we make the case for a vast untapped resource of ancient plant material that is ideally suited for palaeogenomic analyses: Plant remains such as needles, leaves, wood, seeds or fruits that are deposited in natural archives, such as lake sediments, permafrost or even ice caves. Such plant remains are commonly found in large numbers and in stratigraphic sequence through time and have so far been used primarily to reconstruct past local species presences and abundances. However, they are also unique repositories of genetic information with the potential to revolutionize the fields of ecology and evolution by directly studying microevolutionary processes over time. Here, we give an overview of the current state-of-the-art, address important challenges, and highlight new research avenues to inspire future research.

Progressive degeneration of dopaminergic (DA) neurons in the substantia nigra is a hallmark of Parkinson's disease (PD). Dysregulation of developmental transcription factors is implicated in dopaminergic neurodegeneration, but the underlying molecular mechanisms remain largely unknown. Drosophila Fer2 is a prime example of a developmental transcription factor required for the birth and maintenance of midbrain DA neurons. Using an approach combining ChIP-seq, RNA-seq, and genetic epistasis experiments with PD-linked genes, here we demonstrate that Fer2 controls a transcriptional network to maintain mitochondrial structure and function, and thus confers dopaminergic neuroprotection against genetic and oxidative insults. We further show that conditional ablation of Nato3, a mouse homolog of Fer2, in differentiated DA neurons causes mitochondrial abnormalities and locomotor impairments in aged mice. Our results reveal the essential and conserved role of Fer2 homologs in the mitochondrial maintenance of midbrain DA neurons, opening new perspectives for modeling and treating PD.

Recent studies highlighted that exposure to glyphosate can affect specific members of the core gut microbiota of honey bee workers. However, in this study, bees were exposed to relatively high glyphosate concentrations. Here, we chronically exposed newly emerged honey bees to imidacloprid, glyphosate and difenoconazole, individually and in a ternary mixture, at an environmental concentration of 0.1 µg/L. We studied the effects of these exposures on the establishment of the gut microbiota, the physiological status, the longevity, and food consumption of the host. The core bacterial species were not affected by the exposure to the three pesticides. Negative effects were observed but they were restricted to few transient non-core bacterial species. However, in the absence of the core microbiota, the pesticides induced physiological disruption by directly altering the detoxification system, the antioxidant defenses, and the metabolism of the host. Our study indicates that even mild exposure to pesticides can directly alter the physiological homeostasis of newly emerged honey bees and particularly if the individuals exhibit a dysbiosis (i.e. mostly lack the core microbiota). This highlights the importance of an early establishment of a healthy gut bacterial community to strengthen the natural defenses of the honey bee against xenobiotic stressors.

The importance of hybridization and introgression is well documented in the evolution of plants, however, in insects, their role is not fully understood. Given the fact that insects are the most diverse group of organisms, assessing the impact of reticulation events on their evolution may be key to comprehend the emergence of such remarkable diversity. Here, we used an insect model, the Spialia butterflies, to gather genomic evidence of hybridization as a promoter of novel diversity. By using the ddRADseq protocol, we explored the phylogenetic relationships between Spialia orbifer, S. rosae and S. sertorius, and documented two independent events of interspecific gene flow. Our data support that the Iberian endemism S. rosae probably received genetic material from S. orbifer in both mitochondrial and nuclear DNA, which could have contributed to a shift in the ecological preferences of S. rosae. We also show that admixture between S. sertorius and S. orbifer likely occurred in Italy. As a result, the admixed Sicilian populations of S. orbifer are differentiated from the rest of populations both genetically and morphologically, and display signatures of reproductive character displacement in the male genitalia. Additionally, our analyses indicated that genetic material from S. orbifer is present in S. sertorius along the Italian Peninsula. Our findings add to the view that hybridization is a pervasive phenomenon in nature and in butterflies in particular, with important consequences for evolution due to the emergence of novel phenotypes.

Ever since their first report in 1984, Antennapedia-type homeobox (Hox) genes have been involved in such a series of interesting observations, in particular due to their conserved clustered organization between vertebrates and arthropods, that one may legitimately wonder about the origin of this heuristic value. In this essay, I first consider different examples where Hox gene clusters have been instrumental in providing conceptual advances, taken from various fields of research and mostly involving vertebrate embryos. These examples touch upon our understanding of genomic evolution, the revisiting of 19th century views on the relationships between development and evolution and the building of a new framework to understand long-range and pleiotropic gene regulation during development. I then discuss whether the high value of the Hox gene family, when considered as an epistemic object, is related to its clustered structure (and the absence thereof in some animal species) and, if so, what is it in such particular genetic oddities that made them so generous in providing the scientific community with interesting information.

During development, multicellular organisms undergo stereotypical patterns of tissue growth in space and time. How developmental growth is orchestrated remains unclear, largely due to the difficulty of observing and quantitating this process in a living organism. Drosophila histoblast nests are small clusters of progenitor epithelial cells that undergo extensive growth to give rise to the adult abdominal epidermis and are amenable to live imaging. Our quantitative analysis of histoblast proliferation and tissue mechanics reveals that tissue growth is driven by cell divisions initiated through basal extracellular matrix degradation by matrix metalloproteases secreted by the neighboring larval epidermal cells. Laser ablations and computational simulations show that tissue mechanical tension does not decrease as the histoblasts fill the abdominal epidermal surface. During tissue growth, the histoblasts display oscillatory cell division rates until growth termination occurs through the rapid emergence of G0/G1 arrested cells, rather than a gradual increase in cell-cycle time as observed in other systems such as the Drosophila wing and mouse postnatal epidermis. Different developing tissues can therefore achieve their final size using distinct growth termination strategies. Thus, adult abdominal epidermal development is characterized by changes in the tissue microenvironment and a rapid exit from the cell cycle.