Nourissat G.,Service de Chirurgie Orthopedique et Traumatologique |
Berenbaum F.,Service de Rhumatologie |
Duprez D.,CNRS Developmental Biology Laboratory
Nature Reviews Rheumatology | Year: 2015
Tendon is a crucial component of the musculoskeletal system. Tendons connect muscle to bone and transmit forces to produce motion. Chronic and acute tendon injuries are very common and result in considerable pain and disability. The management of tendon injuries remains a challenge for clinicians. Effective treatments for tendon injuries are lacking because the understanding of tendon biology lags behind that of the other components of the musculoskeletal system. Animal and cellular models have been developed to study tendon-cell differentiation and tendon repair following injury. These studies have highlighted specific growth factors and transcription factors involved in tenogenesis during developmental and repair processes. Mechanical factors also seem to be essential for tendon development, homeostasis and repair. Mechanical signals are transduced via molecular signalling pathways that trigger adaptive responses in the tendon. Understanding the links between the mechanical and biological parameters involved in tendon development, homeostasis and repair is prerequisite for the identification of effective treatments for chronic and acute tendon injuries. © 2015 Macmillan Publishers Limited. All rights reserved.
Wassmann K.,University Pierre and Marie Curie |
Wassmann K.,CNRS Developmental Biology Laboratory
Cell Cycle | Year: 2013
Meiotic divisions (meiosis I and II ) are specialized cell divisions to generate haploid gametes. The first meiotic division with the separation of chromosomes is named reductional division. The second division, which takes place immediately after meiosis I without intervening S-phase, is equational, with the separation of sister chromatids, similar to mitosis. This meiotic segregation pattern requires the two-step removal of the cohesin complex holding sister chromatids together: cohesin is removed from chromosome arms that have been subjected to homologous recombination in meiosis I and from the centromere region in meiosis II . Cohesin in the centromere region is protected from removal in meiosis I, but this protection has to be removed-deprotected-for sister chromatid segregation in meiosis II . Whereas the mechanisms of cohesin protection are quite well understood, the mechanisms of deprotection have been largely unknown until recently. In this review I summarize our current knowledge on cohesin deprotection. © 2013 Landes Bioscience.
Storelli G.,CNRS Developmental Biology Laboratory |
Defaye A.,CNRS Developmental Biology Laboratory |
Erkosar B.,CNRS Developmental Biology Laboratory |
Hols P.,Catholic University of Leuven |
And 2 more authors.
Cell Metabolism | Year: 2011
There is growing evidence that intestinal bacteria are important beneficial partners of their metazoan hosts. Recent observations suggest a strong link between commensal bacteria, host energy metabolism, and metabolic diseases such as diabetes and obesity. As a consequence, the gut microbiota is now considered a "host" factor that influences energy uptake. However, the impact of intestinal bacteria on other systemic physiological parameters still remains unclear. Here, we demonstrate that Drosophila microbiota promotes larval growth upon nutrient scarcity. We reveal that Lactobacillus plantarum, a commensal bacterium of the Drosophila intestine, is sufficient on its own to recapitulate the natural microbiota growth-promoting effect. L. plantarum exerts its benefit by acting genetically upstream of the TOR-dependent host nutrient sensing system controlling hormonal growth signaling. Our results indicate that the intestinal microbiota should also be envisaged as a factor that influences the systemic growth of its host. © 2011 Elsevier Inc.
Ronsseray S.,CNRS Developmental Biology Laboratory
Seminars in Cell and Developmental Biology | Year: 2015
Paramutation was initially described in maize and was defined as an epigenetic interaction between two alleles of a locus, through which one allele induces a heritable modification of the other allele without modifying the DNA sequence [1,2]. Thus it implies that the paramutated allele conserves its new properties on the long term over generations even in the absence of the paramutagenic allele and that it turns paramutagenic itself, without undergoing any changes in the DNA sequence. Some epigenetic interactions have been described in two non-vertebrate animal models, which appear to exhibit similar properties. Both systems are linked to trans-generational transmission of non-coding small RNAs. In Drosophila melanogaster, paramutation is correlated with transmission of PIWI-Interacting RNAs (piRNAs), a class of small non-coding RNAs that repress mobile DNA in the germline. A tandem repeated transgenic locus producing abundant ovarian piRNAs can activate piRNA production and associated homology-dependent silencing at a locus that was previously stably devoid of such capacities. The newly converted locus is then perfectly stable in absence of the inducer locus (>100 generations) and becomes fully paramutagenic. In Caenorhabditis elegans, paramutation is correlated with transmission of siRNAs, which are produced by transgenes targeted by piRNAs in the germline. Indeed, a transgenic locus, targeted by the piRNA machinery, produces siRNAs that can induce silencing of homologous transgenes, which can be further transmitted in a repressed state over generations despite the absence of the inducer transgenic locus. As in fly, the paramutated locus can become fully paramutagenic, and paramutation can be mediated by cytoplasmic inheritance without transmission of the paramutagenic locus itself. Nevertheless, in contrast to flies where the induction is only maternally inherited, both parents can transmit it in worms. In addition, a reciprocal phenomenon - (from off toward on) - appears to be also possible in worms as some activated transgenes can reactivate silent transgenes in the germline, and this modification can also be transmitted to next generations, even so it appears to be only partially stable. Thus, in a given system, opposite paramutation-like phenomena could exist, mediated by antagonist active pathways. As in plants, paramutation in flies and worms correlates with chromatin structure modification of the paramutated locus. In flies, inheritance of small RNAs from one generation to the next transmits a memory mainly targeting loci for repression whereas in worms, small RNAs can target loci either for repression or expression. Nevertheless, in the two species, paramutation can play an important role in the epigenome establishment. © 2015 Elsevier Ltd.
Crozatier M.,CNRS Developmental Biology Laboratory |
Vincent A.,CNRS Developmental Biology Laboratory
DMM Disease Models and Mechanisms | Year: 2011
Vertebrate haematopoietic stem cells (HSCs) give rise to a hierarchically organised set of progenitors for erythroid, myeloid, lymphoid and megakaryocyte lineages, and are responsible for lifelong maintenance of the blood system. Dysregulation of the haematopoietic differentiation programme is at the origin of numerous pathologies, including leukaemias. With the discoveries that many transcriptional regulators and signalling pathways controlling blood cell development are conserved between humans and Drosophila melanogaster, the fruit fly has become a good model for investigating the mechanisms underlying the generation of blood cell lineages and blood cell homeostasis. In this review article, we discuss how genetic and molecular studies of Drosophila haematopoiesis can contribute to our understanding of the haematopoietic niche, as well as of the origin and/or progression of haematopoietic malignancies in humans. © 2011. Published by The Company of Biologists Ltd.
Luxardi G.,CNRS Developmental Biology Laboratory |
Marchal L.,CNRS Developmental Biology Laboratory |
Thome V.,CNRS Developmental Biology Laboratory |
Kodjabachina L.,CNRS Developmental Biology Laboratory
Development | Year: 2010
The vertebrate body plan is established in two major steps. First, mesendoderm induction singles out prospective endoderm, mesoderm and ectoderm progenitors. Second, these progenitors are spatially rearranged during gastrulation through numerous and complex movements to give rise to an embryo comprising three concentric germ layers, polarised along dorsoventral, anteroposterior and left-right axes. Although much is known about the molecular mechanisms of mesendoderm induction, signals controlling gastrulation movements are only starting to be revealed. In vertebrates, Nodal signalling is required to induce the mesendoderm, which has precluded an analysis of its potential role during the later process of gastrulation. Using time-dependent inhibition, we show that in Xenopus, Nodal signalling plays sequential roles in mesendoderm induction and gastrulation movements. Nodal activity is necessary for convergent extension in axial mesoderm and for head mesoderm migration. Using morpholino-mediated knockdown, we found that the Nodal ligands Xnr5 and Xnr6 are together required for mesendoderm induction, whereas Xnr1 and Xnr2 act later to control gastrulation movements. This control is operated via the direct regulation of key movement-effector genes, such as papc, has2 and pdgfr.. Interestingly, however, Nodal does not appear to mobilise the Wnt/PCP pathway, which is known to control cell and tissue polarity. This study opens the way to the analysis of the genetic programme and cell behaviours that are controlled by Nodal signalling during vertebrate gastrulation. It also provides a good example of the sub-functionalisation that results from the expansion of gene families in evolution. © 2010. Published by The Company of Biologists Ltd.
Puyaubert J.,CNRS Developmental Biology Laboratory |
Baudouin E.,CNRS Developmental Biology Laboratory
Plant, Cell and Environment | Year: 2014
Low temperature is among the most frequent stresses met by plants during their lifespan, and a plant's ability to cold-acclimate is a determinant for further growth and development. Although intensive research has provided a good picture of the molecular and metabolic changes triggered by cold, the underlying regulatory mechanisms remain elusive and are thus being actively sought. Recent studies have shed light on the importance of nitric oxide (NO), a ubiquitous signalling molecule in eukaryotes, for plant tolerance to chilling and freezing. Indeed, NO formation following cold exposure has been reported in a range of plant species, and a series of proteins targeted by NO-based post-translational modifications have been identified. Moreover, key cold-regulated genes have been characterized as NO-dependent, suggesting the crucial importance of NO signalling for cold-responsive gene expression. This review provides a picture of our current understanding of the function of NO in the context of plant response to cold. Particular attention is dedicated to the open questions left by the fragmented data currently available concerning NO formation, transduction and biological significance for plant adaptation to low temperature. © 2014 John Wiley and Sons Ltd.
On the border of the homeotic function: Re-evaluating the controversial role of cofactor-recruiting motifs: The role of cofactor-recruiting motifs in conferring Hox evolutionary flexibility may critically depend on the protein environment
Merabet S.,CNRS Developmental Biology Laboratory |
Hudry B.,CNRS Developmental Biology Laboratory
BioEssays | Year: 2011
In this review we present concepts that challenge a recently emerging paradigm explaining how similar Hox proteins perform different developmental functions across evolution, despite relatively limited sequence variability. This paradigm relates to the transcription factor, Fushi tarazu (Ftz), whose evolutionary plasticity has been shown to rely on the shuffling between two short protein recognition motifs. We discuss the Ftz paradigm and consider alternative interpretations to the evolutionary flexibility of this Hox protein. In particular, we propose that the protein environment might have played a critical role in the functional shuffling of Ftz during arthropod evolution. © 2011 WILEY Periodicals, Inc.
Gabory A.,CNRS Developmental Biology Laboratory |
Attig L.,CNRS Developmental Biology Laboratory |
Junien C.,CNRS Developmental Biology Laboratory
American Journal of Clinical Nutrition | Year: 2011
The ways in which epigenetic modifications fix the effects of early environmental events, ensuring sustained responses to transient stimuli that result in modified gene expression patterns and phenotypes later in life, are a topic of considerable interest. This article focuses on recently discovered mechanisms and calls into question prevailing views about the dynamics, positions, and functions of epigenetic marks. Most epigenetic studies have addressed the long-term effects of environmental stressors on a small number of epigenetic marks, at the global or individual gene level, in humans and in animal models. In parallel, increasing numbers of studies based on high-throughput technologies are revealing additional complexity in epigenetic processes by highlighting the importance of crosstalk between different epigenetic marks in humans and mice. A number of studies focusing on metabolic programming and the developmental origin of health and disease have identified links between early nutrition, epigenetic processes, and long-term illness. The existence of a self-propagating epigenetic cycle has been shown. Moreover, recent studies have shown an obvious sexual dimorphism both for programming trajectories and in response to the same environmental insult. Despite recent progress, however, we are still far from understanding how, when, and where environmental stressors disturb key epigenetic mechanisms. Thus, the need to identify original key marks and monitor the changes they undergo throughout development, during an individual's lifetime, or over several generations remains a challenging issue. © 2011 American Society for Nutrition.
Peret B.,CNRS Developmental Biology Laboratory |
Clement M.,CNRS Developmental Biology Laboratory |
Nussaume L.,CNRS Developmental Biology Laboratory |
Desnos T.,CNRS Developmental Biology Laboratory
Trends in Plant Science | Year: 2011
Phosphorus is a crucial component of major organic molecules such as nucleic acids, ATP and membrane phospholipids. It is present in soils in the form of inorganic phosphate (Pi), which has low availability and poor mobility. To cope with Pi limitations, plants have evolved complex adaptive responses that include morphological and physiological modifications. This review describes how the model plant Arabidopsis thaliana adapts its root system architecture to phosphate deficiency through inhibition of primary root growth, increase in lateral root formation and growth and production of root hairs, which all promote topsoil foraging. A better understanding of plant adaptation to low phosphate will open the way to increased phosphorus use efficiency by crops. Such an improvement is needed in order to adjust how we manage limited phosphorus stocks and to reduce the disastrous environmental effects of phosphate fertilizers overuse. © 2011 Elsevier Ltd.