CNRS Lyon Institute of Functional Genomics

Lyon, France

CNRS Lyon Institute of Functional Genomics

Lyon, France
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Guillon E.,CNRS Lyon Institute of Functional Genomics | Bretaud S.,CNRS Lyon Institute of Functional Genomics | Ruggiero F.,CNRS Lyon Institute of Functional Genomics
Journal of Neuroscience | Year: 2016

The extracellular matrix (ECM) provides local positional information to guide motoneuron axons toward their muscle target. Collagen XV is a basement membrane component mainly expressed in skeletal muscle. We have identified two zebrafish paralogs of the humanCOL15A1gene,col15a1aandcol15a1b, which display distinct expression patterns. Here we show thatcol15a1bis expressed and deposited in the motor path ECM by slow muscle precursors also called adaxial cells. We further demonstrate that collagen XV-B deposition is both temporally and spatially regulated before motor axon extension from the spinal cord in such a way that it remains in this region after the adaxial cells have migrated toward the periphery of the myotome. Loss- and gain-of-function experiments in zebrafish embryos demonstrate thatcol15a1bexpression and subsequent collagen XV-B deposition and organization in the motor path ECM depend on a previously undescribed two-step mechanism involving Hedgehog/Gli andunplugged/MuSK signaling pathways.In silicoanalysis predicts a putative Gli binding site in thecol15a1bproximal promoter. Usingcol15a1bpromoter-reporter constructs, we demonstrate thatcol15a1bparticipates in the slow muscle genetic program as a direct target of Hedgehog/Gli signaling. Loss and gain ofcol15a1bfunction provoke pathfinding errors in primary and secondary motoneuron axons both at and beyond the choice point where axon pathway selection takes place. These defects result in muscle atrophy and compromised swimming behavior, a phenotype partially rescued by injection of asmyhc1:col15a1bconstruct. These reveal an unexpected and novel role for collagen XV in motor axon pathfinding and neuromuscular development. © 2016 the authors.


Marchi N.,Cleveland Clinic | Marchi N.,CNRS Lyon Institute of Functional Genomics | Granata T.,Carlo Besta Neurologic Institute | Janigro D.,Cleveland Clinic
Trends in Neurosciences | Year: 2014

Epilepsy refers to a cluster of neurological diseases characterized by seizures. Although many forms of epilepsy have a well-defined immune etiology, in other forms of epilepsy an altered immune response is only suspected. In general, the hypothesis that inflammation contributes to seizures is supported by experimental results. Additionally, antiepileptic maneuvers may act as immunomodulators and anti-inflammatory therapies can treat seizures. Triggers of seizure include a bidirectional communication between the nervous system and organs of immunity. Thus, a crucial cellular interface protecting from immunological seizures is the blood-brain barrier (BBB). Here, we summarize recent advances in the understanding and treatment of epileptic seizures that derive from a non-neurocentric viewpoint and suggest key avenues for future research. © 2013 Elsevier Ltd.


Staquet M.J.,CNRS Lyon Institute of Functional Genomics
Advances in dental research | Year: 2011

Initial sensing of infection is mediated by germline-encoded pattern-recognition receptors (PRRs), the activation of which leads to the expression of inflammatory mediators responsible for the elimination of pathogens and infected cells. PRRs act as immune sensors that provide immediate cell responses to pathogen invasion or tissue injury. Here, we review the expression of PRRs in human dental pulp cells, namely, receptors from the Toll-like (TLR) and Nod-like NLR families, by which cells recognize bacteria. Particular attention is given to odontoblasts, which are the first cells encountered by pathogens and represent, in the tooth, the first line of defense for the host. Understanding cellular and molecular mechanisms associated with the recognition of bacterial pathogens by odontoblasts is critical for the development of therapeutic strategies that aim at preventing excessive pulp inflammation and related deleterious effects.


Sirakov M.,CNRS Lyon Institute of Functional Genomics | Plateroti M.,CNRS Lyon Institute of Functional Genomics
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2011

The thyroid hormones control the development and the homeostasis of several organs in vertebrates. Their actions depend, for the most part, on nuclear receptors, the TRs, which are transcription factors whose activity is modulated by the hormone T3. The gastrointestinal tract is a well characterized target of thyroid hormones and TRs, as extensively described in the literature. In fact, its remodeling in amphibians during thyroid hormone-dependent metamorphosis is well characterized at the cellular and the molecular levels. However, whereas a great attention has been paid to the nervous system and to cardiac development and physiology, the function of thyroid hormones and TRs in the mammalian gastrointestinal tract has been, until recently, underestimated. Several studies have described an important conservation of this hormonal signal during intestinal development and have suggested that it may play a role in stem cell physiology in both amphibians and mammals. These findings show the importance of the thyroid hormones and TRs, whose homologous actions are maintained across species. In the present review, we summarize the most recent data on this issue, starting from work that has been conducted on amphibian metamorphosis to results on postnatal development, homeostasis, and tumorigenesis in mammals. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease. © 2010 Elsevier B.V.


Flamant F.,CNRS Lyon Institute of Functional Genomics | Gauthier K.,CNRS Lyon Institute of Functional Genomics
Biochimica et Biophysica Acta - General Subjects | Year: 2013

Background: Thyroid hormone receptors TRα1, TRβ1 and TRβ2 are broadly expressed and exert a pleiotropic influence on many developmental and homeostatic processes. Extensive genetic studies in mice precisely defined their respective function. Scope of review: The purpose of the review is to discuss two puzzling issues:The isoform specificity problem: the different functions of TRα1, TRβ1 and TRβ2 might reflect either their different distribution in tissues or differences in the receptor intrinsic properties.The cell-specificity problem: one would expect that different cell types share a common repertoire of TR target genes, but current knowledge does not support this assumption. How TR function is affected by the cellular context is an unsolved question. Major conclusions: Mouse genetics support a balanced contribution of expression pattern and receptor intrinsic properties in defining the receptor respective functions. The molecular mechanisms sustaining cell specific response remain hypothetical and based on studies performed with other nuclear receptors. General significance: The isoform-specificity and cell-specificity questions have many implications for clinical research, drug development, and endocrine disruptor studies. This article is part of a Special Issue entitled Thyroid hormone signalling. © 2012 Elsevier B.V. All rights reserved.


Theodosiou M.,CNRS Lyon Institute of Functional Genomics | Laudet V.,CNRS Lyon Institute of Functional Genomics | Schubert M.,CNRS Lyon Institute of Functional Genomics
Cellular and Molecular Life Sciences | Year: 2010

Vitamin A is essential for the formation and maintenance of many body tissues. It is also important for embryonic growth and development and can act as a teratogen at critical periods of development. Retinoic acid (RA) is the biologically active form of vitamin A and its signaling is mediated by the RA and retinoid X receptors. In addition to its role as an important molecule during development, RA has also been implicated in clinical applications, both as a potential anti-tumor agent as well as for the treatment of skin diseases. This review presents an overview of how dietary retinoids are converted to RA, hence presenting the major players in RA metabolism and signaling, and highlights examples of treatment applications of retinoids. Moreover, we discuss the origin and diversification of the retinoid pathway, which are important factors for understanding the evolution of ligand-specificity among retinoid receptors. © 2010 Birkhäuser Verlag.


Sadier A.,CNRS Lyon Institute of Functional Genomics | Viriot L.,CNRS Lyon Institute of Functional Genomics | Pantalacci S.,CNRS Lyon Institute of Functional Genomics | Laudet V.,CNRS Lyon Institute of Functional Genomics
Trends in Genetics | Year: 2014

The ectodysplasin (EDA) pathway, which is active during the development of ectodermal organs, including teeth, hairs, feathers, and mammary glands, and which is crucial for fine-tuning the developmental network controlling the number, size, and density of these structures, was discovered by studying human patients affected by anhidrotic/hypohidrotic ectodermal dysplasia. It comprises three main gene products: EDA, a ligand that belongs to the tumor necrosis factor (TNF)-α family, EDAR, a receptor related to the TNFα receptors, and EDARADD, a specific adaptor. This core pathway relies on downstream NF-κB pathway activation to regulate target genes. The pathway has recently been found to be associated with specific adaptations in natural populations: the magnitude of armor plates in sticklebacks and the hair structure in Asian human populations. Thus, despite its role in human disease, the EDA pathway is a 'hopeful pathway' that could allow adaptive changes in ectodermal appendages which, as specialized interfaces with the environment, are considered hot-spots of morphological evolution. © 2013 Elsevier Ltd.


Bleicher F.,CNRS Lyon Institute of Functional Genomics
Experimental Cell Research | Year: 2014

Odontoblasts are post-mitotic cells organized as a layer of palisade cells along the interface between the dental pulp and dentin. They are responsible for the formation of the physiological primary and secondary dentins. They synthesize the organic matrix of type I collagen and actively participate to its mineralization by secreting proteoglycans and non-collagenous proteins that are implicated in the nucleation and the control of the growth of the mineral phase. They also participate to the maintenance of this hard tissue throughout the life of the tooth by synthesizing reactionary dentin in response to pathological conditions (caries, attrition, erosion. . .).Besides these fundamental dentinogenic activities, odontoblasts were recently suspected to play a role as sensor cells. They are able to sense the bacteria invasion during caries and then to initiate the pulp immune and inflammatory response. They are also well equipped in ion channels implicated in mechanotransduction or nociception which make odontoblasts suitable candidates to sense external stimuli and to mediate tooth pain sensation. © 2013 Elsevier Inc.


Laudet V.,CNRS Lyon Institute of Functional Genomics
Current Biology | Year: 2011

Metamorphosis, classically defined as a spectacular post-embryonic transition, is well exemplified by the transformation of a tadpole into a frog. It implies the appearance of new body parts (such as the limbs), the resorption of larval features (such as the tail) and the remodelling of many organs (such as the skin or the intestine). In vertebrates, metamorphosis has been well characterized in anuran amphibians, where thyroid hormones orchestrate the intricate and seemingly contradictory changes observed at the cellular and tissue levels. Thyroid hormones control a complex hierarchical cascade of target genes via binding to specific receptors, TRα and TRβ, ligand-activated transcription factors belonging to the nuclear receptor superfamily. Metamorphosis is actually widespread in the vertebrates, though quite diverse in the way it manifests in a particular species. Furthermore, evolutionary and ecological variations of this key event, from paedomorphosis to direct development, provide an excellent illustration of how tinkering with a control pathway can lead to divergent life histories. The study of invertebrate chordates has also shed light on the origin of metamorphosis. The available data suggest that post-embryonic remodelling governed by thyroid hormones is an ancestral feature of chordates. According to this view, metamorphosis of the anurans is an extreme example of a widespread life history transition. © 2011 Elsevier Ltd. All rights reserved.


Louchart A.,CNRS Lyon Institute of Functional Genomics | Viriot L.,CNRS Lyon Institute of Functional Genomics
Trends in Ecology and Evolution | Year: 2011

All living birds are toothless, constituting by far the most diverse toothless vertebrate clade, and are striking examples of evolutionary success following tooth loss. In recent years, an unprecedented number of Mesozoic birds have been described, illustrating the evolution of dentition reductions. Simultaneously, major advances in experimental embryology have yielded new results concerning avian edentulism. Reviewing these lines of evidence, we propose hypotheses for its causes, with a prominent role for the horny beak during development. A horny beak and a muscular gizzard functionally 'replaced' dentition for food acquisition and processing, respectively. Together with edentulism itself, these features and others contributed to the later success of birds, as a result of their high performance or additional functionality working in concert in these complex organisms. © 2011 Elsevier Ltd.

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