Publications

The synchronous cleavage divisions of early embryogenesis require coordination of the cell-cycle oscillator, the dynamics of the cytoskeleton, and the cytoplasm. Yet, it remains unclear how spatially restricted biochemical signals are integrated with physical properties of the embryo to generate collective dynamics. Here, we show that synchronization of the cell cycle in Drosophila embryos requires accurate nuclear positioning, which is regulated by the cell-cycle oscillator through cortical contractility and cytoplasmic flows. We demonstrate that biochemical oscillations are initiated by local Cdk1 inactivation and spread through the activity of phosphatase PP1 to generate cortical myosin II gradients. These gradients cause cortical and cytoplasmic flows that control proper nuclear positioning. Perturbations of PP1 activity and optogenetic manipulations of cortical actomyosin disrupt nuclear spreading, resulting in loss of cell-cycle synchrony. We conclude that mitotic synchrony is established by a self-organized mechanism that integrates the cell-cycle oscillator and embryo mechanics.

We introduce a model for the mass transfer of molecular activators and inhibitors in two media separated by an interface, and study its interaction with the deformations exhibited by the two-layer skin tissue where they occur. The mathematical model results in a system of nonlinear advection-diffusion–reaction equations including cross-diffusion, and coupled with an interface elasticity problem. We propose a Galerkin method for the discretisation of the set of governing equations, involving also a suitable Newton linearisation, partitioned techniques, non-overlapping Schwarz alternating schemes, and high-order adaptive time stepping algorithms. The experimental accuracy and robustness of the proposed partitioned numerical methods is assessed, and some illustrating tests in 2D and 3D are provided to exemplify the coupling effects between the mechanical properties and the advection-diffusion–reaction interactions involving the two separate layers.

Hypostomus commersoni Valenciennes 1836, Hypostomus cordovae (Günther 1880) and Hypostomus laplatae (Eigenmann 1907) have been little studied since their original descriptions. This study shows a comprehensive review of these species from the Lower La Plata Basin, including their taxonomic history, distribution, color patterns, morphology, and ecological and molecular phylogenetic data. Morphological and phylogenetic analyses based on D-loop sequences suggested that H. commersoni can be separated into two subclades, or subgroups. Based on these results and on the non-overlapping distribution range of the two subclades, we conclude that they represent two distinct species, thereby revalidating H. spiniger. The results also suggest that H. paranensis should be considered as species inquirenda and H. cordovae as valid species. This integrated approach provides key information for assessing the conservation status and biogeographic aspects of the genus Hypostomus in the Lower La Plata Basin.

Bacterial symbionts are known to facilitate a wide range of physiological processes and ecological interactions for their hosts. In spite of this, caterpillars with highly diverse life histories appear to lack resident microbiota. Gut physiology, endogenous digestive enzymes, and limited social interactions may contribute to this pattern, but the consequences of shifts in social activity and diet on caterpillar microbiota are largely unknown. caterpillars undergo particularly dramatic social and dietary shifts when they parasitize ant colonies, rapidly transitioning from solitary herbivory to ant tending (i.e., receiving protein-rich regurgitations through trophallaxis). This unique life history provides a model for studying interactions between social living, diet, and caterpillar microbiota. Here, we characterized and compared bacterial communities within .  caterpillars before and after their association with ants, using 16S rRNA amplicon sequencing and quantitative PCR. After being adopted by ants, bacterial communities within caterpillars shifted substantially, with a significant increase in alpha diversity and greater consistency in bacterial community composition in terms of beta dissimilarity. We also characterized the bacterial communities within their host ants (), food plant (), and soil from ant nest chambers. These data indicated that the aforementioned patterns were influenced by bacteria derived from caterpillars' surrounding environments, rather than through transfers from ants. Thus, while bacterial communities are substantially reorganized over the life cycle of caterpillars, it appears that they do not rely on transfers of bacteria from host ants to complete their development.

In response to extracellular signals, many signalling proteins associated with the plasma membrane are sorted into endosomes. This involves endosomal fusion, which depends on the complexes HOPS and CORVET. Whether and how their subunits themselves modulate signal transduction is unknown. We show that Vps11 and Vps18 (Vps11/18), two common subunits of the HOPS/CORVET complexes, are E3 ubiquitin ligases. Upon overexpression of Vps11/Vps18, we find perturbations of ubiquitination in signal transduction pathways. We specifically demonstrate that Vps11/18 regulate several signalling factors and pathways, including Wnt, estrogen receptor α (ERα), and NFκB. For ERα, we demonstrate that the Vps11/18-mediated ubiquitination of the scaffold protein PELP1 impairs the activation of ERα by c-Src. Thus, proteins involved in membrane traffic, in addition to performing their well-described role in endosomal fusion, fine-tune signalling in several different ways, including through ubiquitination.

Many species of snakes exhibit epidermal surface nanostructures that form complex motifs conferring self-cleaning properties, and sometimes structural iridescence, to their skin.

PMEL is a pigment cell-specific protein that forms a functional amyloid matrix in melanosomes. The matrix consists of well-separated fibrillar sheets on which the pigment melanin is deposited. Using electron tomography, we demonstrate that this sheet architecture is governed by the PMEL repeat (RPT) domain, which associates with the amyloid as an accessory proteolytic fragment. Thus, the RPT domain is dispensable for amyloid formation as such but shapes the morphology of the matrix, probably in order to maximize the surface area available for pigment adsorption. Although the primary amino acid sequence of the RPT domain differs vastly among various vertebrates, we show that it is a functionally conserved, interchangeable module. RPT domains of all species are predicted to be very highly O-glycosylated, which is likely the common defining feature of this domain. O-glycosylation is indeed essential for RPT domain function and the establishment of the PMEL sheet architecture. Thus, O-glycosylation, not amino acid sequence, appears to be the major factor governing the characteristic PMEL amyloid morphology.

HLA matching is a critical factor for successful allogeneic hematopoietic stem cell transplantation. For unrelated donor searches, matching is usually based on high-resolution typing at five HLA loci, looking for a 10/10 match. Some studies have proposed that further matching at the haplotype level could be beneficial for clinical outcome. In this study, we determined the phased haplotypes of 291 patients using family members and segregation analysis. The sum of ranks of the haplotypes carried by patients was used as a surrogate predictor of a successful unrelated donor search. The putative impact of haplotypes was then analyzed in a cohort of 211 recipients transplanted with 10/10 matched unrelated donors. A logistic regression analysis showed a highly significant effect of the haplotypes in the outcome of a search, but we did not find any significant effect on overall survival, graft versus host disease or relapse/progression following HSCT. This study provides useful data for the optimization of unrelated bone marrow donor searches, but does not confirm previous reports that matching at the haplotype level has a clinical impact following HSCT. Due to the extreme polymorphism of HLA genes, further studies are warranted to better understand the many factors at play.

In Hydra the nervous system is composed of neurons and mechanosensory cells that differentiate from interstitial stem cells (ISCs), which also provide gland cells and germ cells. The adult nervous system is actively maintained through continuous de novo neurogenesis that occurs at two distinct paces, slow in intact animals and fast in regenerating ones. Surprisingly Hydra vulgaris survive the elimination of cycling interstitial cells and the subsequent loss of neurogenesis if force-fed. By contrast, H. oligactis animals exposed to cold temperature undergo gametogenesis and a concomitant progressive loss of neurogenesis. In the cold-sensitive strain Ho_CS, this loss irreversibly leads to aging and animal death. Within four weeks, Ho_CS animals lose their contractility, feeding response, and reaction to light. Meanwhile, two positive regulators of neurogenesis, the homeoprotein prdl-a and the neuropeptide Hym-355, are no longer expressed, while the "old" RFamide-expressing neurons persist. A comparative transcriptomic analysis performed in cold-sensitive and cold-resistant strains confirms the downregulation of classical neuronal markers during aging but also shows the upregulation of putative regulators of neurotransmission and neurogenesis such as AHR, FGFR, FoxJ3, Fral2, Jagged, Meis1, Notch, Otx1, and TCF15. The switch of Fral2 expression from neurons to germ cells suggests that in aging animals, the neurogenic program active in ISCs is re-routed to germ cells, preventing de novo neurogenesis and impacting animal survival.