Publications

Human families with chromosomal rearrangements at 2q31, where the human HOXD locus maps, display mesomelic dysplasia, a severe shortening and bending of the limb. In mice, the dominant Ulnaless inversion of the HoxD cluster produces a similar phenotype suggesting the same origin for these malformations in humans and mice. Here we engineer 1 Mb inversion including the HoxD gene cluster, which positioned Hoxd13 close to proximal limb enhancers. Using this model, we show that these enhancers contact and activate Hoxd13 in proximal cells, inducing the formation of mesomelic dysplasia. We show that a secondary Hoxd13 null mutation in-cis with the inversion completely rescues the alterations, demonstrating that ectopic HOXD13 is directly responsible for this bone anomaly. Single-cell expression analysis and evaluation of HOXD13 binding sites suggests that the phenotype arises primarily by acting through genes normally controlled by HOXD13 in distal limb cells. Altogether, these results provide a conceptual and mechanistic framework to understand and unify the molecular origins of human mesomelic dysplasia associated with 2q31.

Lumen formation plays an essential role in the morphogenesis of tissues during development. Here we review the physical principles that play a role in the growth and coarsening of lumens. Solute pumping by the cell, hydraulic flows driven by differences of osmotic and hydrostatic pressures, balance of forces between extracellular fluids and cell-generated cytoskeletal forces, and electro-osmotic effects have been implicated in determining the dynamics and steady-state of lumens. We use the framework of linear irreversible thermodynamics to discuss the relevant force, time and length scales involved in these processes. We focus on order of magnitude estimates of physical parameters controlling lumen formation and coarsening.

Mammalian genomes are partitioned into sub-megabase to megabase-sized units of preferential interactions called topologically associating domains or TADs, which are likely important for the proper implementation of gene regulatory processes. These domains provide structural scaffolds for distant cis regulatory elements to interact with their target genes within the three-dimensional nuclear space and architectural proteins such as CTCF as well as the cohesin complex participate in the formation of the boundaries between them. However, the importance of the genomic context in providing a given DNA sequence the capacity to act as a boundary element remains to be fully investigated. To address this question, we randomly relocated a topological boundary functionally associated with the mouse HoxD gene cluster and show that it can indeed act similarly outside its initial genomic context. In particular, the relocated DNA segment recruited the required architectural proteins and induced a significant depletion of contacts between genomic regions located across the integration site. The host chromatin landscape was re-organized, with the splitting of the TAD wherein the boundary had integrated. These results provide evidence that topological boundaries can function independently of their site of origin, under physiological conditions during mouse development.

Quantitative expression of the RNA of these 17 genes in normal and cancerous tissues obtained using chip arrays from the public functional genomics data repository, Gene Expression Omnibus (GEO) application, was compared statistically.

The development of the amniote limb has been an important model system to study patterning mechanisms and morphogenesis. For proper growth and patterning, it requires the interaction between the distal sub-apical mesenchyme and the apical ectodermal ridge (AER) that involve the separate implementation of coordinated and tissue-specific genetic programs.

Here we discuss the developmental and homeostatic conditions necessary for regeneration. is characterized by populations of adult stem cells paused in the G2 phase of the cell cycle, ready to respond to injury signals. The body column can be compared to a blastema-like structure, populated with multifunctional epithelial stem cells that show low sensitivity to proapoptotic signals, and high inducibility of autophagy that promotes resistance to stress and starvation. Intact polyps also exhibit a dynamic patterning along the oral-aboral axis under the control of homeostatic organizers whose activity results from regulatory loops between activators and inhibitors. As in bilaterians, injury triggers the immediate production of reactive oxygen species (ROS) signals that promote wound healing and contribute to the reactivation of developmental programs via cell death and the de novo formation of new organizing centers from somatic tissues. In aging , regeneration is rapidly lost as homeostatic conditions are no longer pro-regenerative.

Benthic foraminiferal research in the North Pacific has a long history, with works published over a century ago providing important information about the taxonomy and distribution of morphospecies. These studies focused mainly on areas outside the Clarion-Clipperton Zone (CCZ). Our knowledge of foraminiferal faunas within the CCZ originates largely from recent baseline investigations related to likely future seabed mining of the polymetallic nodule deposits. These have revealed highly diverse assemblages of sediment-dwelling morphospecies among the meiofauna and macrofauna, as well as megafaunal xenophyophores and nodule-attached fauna. Morphological analyses have been complemented by metabarcoding studies that yielded even higher numbers of molecular species (Operational Taxonomic Units - OTUs). Monothalamids, the vast majority undescribed, constitute a substantial proportion of both morphological and molecular datasets, with multichambered agglutinated and calcareous foraminifera being less common. Their importance in this abyssal (>4,000 m depth) habitat likely reflects food limitation combined with carbonate dissolution close to and below the carbonate compensation depth. Literature records, supported in a few cases by genetic data, suggest that many morphospecies found in the CCZ have wide geographical distributions across the Pacific abyss and in other oceans. At smaller spatial scales (several 100s of kilometers) there is a general uniformity in assemblage composition. Nevertheless, many morphospecies are too rare to conclude anything about their geographical distributions. Similarly, the part played by benthic foraminifera in CCZ ecosystems is largely a matter of speculation, although their abundance across different size classes suggests that it is significant. Meiofauna-sized taxa that consume freshly-deposited organic detritus may be important in carbon cycling, particularly at the shallower, more eutrophic eastern end of the CCZ. Megafaunal xenophyophores can provide habitat structure for other organisms, potentially enhancing benthic biodiversity. Foraminifera of all sizes could be among the earliest recolonisers of disturbed or redeposited sediments. Their potential contributions in terms of both ecology and biodiversity make these protists significant members of benthic communities in the CCZ.

The Covid-19 outbreak has triggered a global crisis that is challenging governments, health systems and the scientific community worldwide. A central question in the Covid-19 pandemic is whether climatic factors have influenced its progression. To address this question, we used mortality rates during the first three weeks of recorded mortality in 144 countries, during the first wave of the pandemic. We examined the effect of climatic variables, along with the proportion of the population older than 64 years old, the number of beds in hospitals, and the timing and strength of the governmental travel measures to control the spread of the disease. Our first model focuses on air temperature as the central climatic factor and explains 67% of the variation in mortality rate, with 37% explained by the fixed variables considered and 31% explained by country-specific variations. We show that mortality rate is negatively influenced by warmer air temperature. Each additional Celsius degree decreases mortality rate by ~5%. Our second model is centred on the UV Index and follows the same trend as air temperature, explaining 69% of the variation in mortality rate. These results are robust to the exclusion of countries with low incomes, as well as to the exclusion of low- and medium-income countries. We also show that the proportion of vulnerable age classes and access to healthcare are critical factors impacting the mortality rate of this disease. The effects of air temperature at an early stage of the Covid-19 outbreak is a key factor to understand the primary spread of this pandemic, and should be considered in projecting subsequent waves.

The distribution of genetic diversity across a species distribution range is rarely homogeneous, as the genetic structure among populations is related to the degree of isolation among them, such as isolation by distance, isolation by barrier, and isolation by environment. is a small viviparous fish that inhabits a wide range of habitats in South America. To decipher the isolation processes that drive population structuring in we analyzed 221 sequences of the mitochondrial (COI), from 19 localities. Then, we examined the influence of the three most common types of isolation in order to explain the genetic variation found in this species.Our results revealed a marked structuration, with three groups: (a) La Plata/Desaguadero Rivers (sampling sites across Argentina, Uruguay, and Southern Brazil), (b) Central Argentina, and (c) Northern Argentina. A distance-based redundancy analysis, including the explanatory variables geographical distances, altitude, latitude, and basin, was able to explain up to 65% of the genetic structure. A variance partitioning analysis showed that the two most important variables underlying the structuration in were altitude (isolation by environment) and type of basin (isolation by barrier).Our results show that in this species, the processes of population diversification are complex and are not limited to a single mechanism. The processes that play a prominent role in this study could explain the high rate of diversity that characterizes freshwater fish species. And these processes in turn are the basis for possible speciation events.

Actinopterygians (ray-finned fishes) are the most diversified group of vertebrates and are characterized by a variety of protective structures covering their integument, the evolution of which has intrigued biologists for decades. Paleontological records showed that the first mineralized vertebrate skeleton was composed of dermal bony plates covering the body, including odontogenic and skeletogenic components. Later in evolution, the exoskeleton of actinopterygian's trunk was composed of scale structures. Although scales are nowadays a widespread integument cover, some contemporary lineages do not have scales but bony plates covering their trunk, whereas other lineages are devoid of any such structures. To understand the evolution of the integument coverage and particularly the transition between different structures, we investigated the pattern of scale loss events along with actinopterygian evolution and addressed the functional relationship between the scaleless phenotype and the ecology of fishes. Furthermore, we examined whether the emergence of trunk bony plates was dependent over the presence or absence of scales. To this aim, we used two recently published actinopterygian phylogenies, one including >11,600 species, and by using stochastic mapping and Bayesian methods, we inferred scale loss events and trunk bony plate acquisitions. Our results reveal that a scaled integument is the most frequent state in actinopterygians, but multiple independent scale loss events occurred along their phylogeny with essentially no scale re-acquisition. Based on linear mixed models, we found evidence supporting that after a scale loss event, fishes tend to change their ecology and adopt a benthic lifestyle. Furthermore, we show that trunk bony plates appeared independently multiple times along the phylogeny. By using fitted likelihood models for character evolution, we show that trunk bony plate acquisitions were dependent on a previous scale loss event. Overall, our findings support the hypothesis that integument cover is a key evolutionary trait underlying actinopterygian radiation.