Publications

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.

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.