A5013768879- Retinal Development and Disorders
- Retinal Diseases and Treatments
- Hippo pathway signaling and YAP/TAZ
- Photoreceptor and optogenetics research
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Research and Splicing
- Photochromic and Fluorescence Chemistry
- Cellular transport and secretion
- RNA regulation and disease
- Ubiquitin and proteasome pathways
- Retinopathy of Prematurity Studies
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Olfactory and Sensory Function Studies
- interferon and immune responses
- Glaucoma and retinal disorders
- Ophthalmology and Visual Impairment Studies
- bioluminescence and chemiluminescence research
- Muscle Physiology and Disorders
- Retinal Imaging and Analysis
- Wnt/β-catenin signaling in development and cancer
- Microtubule and mitosis dynamics
- Circadian rhythm and melatonin
- Neuroscience and Neuropharmacology Research
- Developmental Biology and Gene Regulation
Université Paris-Saclay
2015-2024
Institut des Neurosciences Paris-Saclay
2015-2024
Centre National de la Recherche Scientifique
2015-2024
CEA Paris-Saclay
2020-2024
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2020-2024
Retina France
2015-2024
Centre Ophtalmologique d'Imagerie et de Laser
2015-2024
National Institutes of Health
2009-2021
National Eye Institute
2009-2021
Inserm
2003-2019
Microglia, the principal resident immune cell of CNS, exert significant influence on neurons during development and in pathological situations. However, if how microglia contribute to normal neuronal function mature uninjured CNS is not well understood. We used model adult mouse retina, a part amenable structural functional analysis, investigate constitutive role by depleting from retina sustained manner using genetic methods. discovered that are acutely required for maintenance retinal...
Chemokine signaling via CX3CL1-CX3CR1 helps regulate homeostasis in the population of microglia adult mouse retina.
Contrasting with fish or amphibian, retinal regeneration from Müller glia is largely limited in mammals. In our quest toward the identification of molecular cues that may boost their stemness potential, we investigated involvement Hippo pathway effector YAP (Yes-associated protein), which upregulated cells following injury. Conditional Yap deletion mouse prevents cell-cycle gene upregulation normally accompanies reactive gliosis upon photoreceptor cell death. We further show that, Xenopus, a...
The aim of this study was to examine the effects supplementation with n-3 polyunsaturated fatty acids (PUFAs) on stress responses in mice subjected an unpredictable chronic mild (UCMS) procedure. Stress-induced modifications coat and aggressiveness were evaluated, phospholipid PUFA profiles monoamine levels analyzed frontal cortex, hippocampus, striatum. results showed that repeated exposure stressors induced degradation physical state coat, lowered body weight gain, increased...
Leber congenital amaurosis (LCA) encompasses a set of early-onset blinding diseases that are characterized by vision loss, involuntary eye movement, and nonrecordable electroretinogram (ERG). At least 19 genes associated with LCA, which is typically recessive; however, mutations in homeodomain transcription factor CRX lead to an autosomal dominant form LCA. The mechanism CRX-associated LCA not understood. Here, we identified spontaneous mouse mutant frameshift mutation Crx (CrxRip). We...
Abstract Mutations in the ubiquitously expressed pre-mRNA processing factor ( PRPF ) 31 gene, one of most common causes dominant form Retinitis Pigmentosa (RP), lead to a retina-specific phenotype. It is uncertain which retinal cell types are affected and animal models do not clearly present RP phenotype observed PRPF31 patients. Retinal organoids pigment epithelial (RPE) cells derived from human-induced pluripotent stem (iPSCs) provide potential opportunities for studying human -related RP....
Purpose: During retinal degeneration, Müller glia cells respond to photoreceptor loss by undergoing reactive gliosis, with both detrimental and beneficial effects. Increasing our knowledge of the complex molecular response degeneration is thus essential for development new therapeutic strategies. The purpose this work was identify factors involved in cell death. Methods: Whole transcriptome sequencing performed from wild-type degenerating rd10 mouse retinas at P30. changes mRNA abundance...
The orphan nuclear receptor NR2E3 is a direct transcriptional target of NRL, the key basic motif leucine zipper transcription factor that dictates rod versus cone photoreceptor cell fate in mammalian retina. lack function humans and retinal degeneration rd7 mutant mouse leads to increased S-cones accompanied by degeneration, whereas ectopic expression Nr2e3 cone-only Nrl−/− retina generates rod-like cells do not exhibit any visual function. Using GFP tag newborn rods 5-bromo-2′-deoxyuridine...
Cone photoreceptors are the primary initiator of visual transduction in human retina. Dysfunction or death rod precedes cone loss many retinal and macular degenerative diseases, suggesting a rod-dependent trophic support for survival. Rod differentiation homeostasis dependent on basic motif leucine zipper transcription factor neural retina (NRL). The Nrl ( −/− ) mice results with predominantly S-opsin-containing cones that exhibit molecular functional characteristics wild-type cones. Here,...
Abstract Cone photoreceptor cell death in inherited retinal diseases, such as Retinitis Pigmentosa (RP), leads to the loss of high acuity and color vision and, ultimately blindness. In RP, a vast number mutations perturb structure function rod photoreceptors, while cones remain initially unaffected. Extensive advanced stages disease triggers cone by mechanism that is still largely unknown. Here, we show secondary animal models for RP associated with increased activity histone deacetylates...
BACKGROUND. This study systematically investigated circulating and retinal tissue lipid determinants of human diabetic retinopathy (DR) to identify underlying alterations associated with severity DR.
Dystrophin Dp71 is the major product of Duchenne muscular dystrophy (DMD) gene in brain, and its loss DMD patients mouse models leads to cognitive impairments. expressed as a range proteins generated by alternative splicing exons 71 74 78, classified main Dp71d Dp71f groups that contain specific C-terminal ends. However, it unknown whether each isoform has role distinct cell types, brain regions, and/or stages development. In present study, we characterized expression isoforms during fetal...
Development of rod photoreceptors in the mammalian retina is critically dependent on basic motif-leucine zipper transcription factor NRL (neural leucine zipper). In absence NRL, photoreceptor precursors mouse produce only cones that primarily express S-opsin. Conversely, ectopic expression post-mitotic leads to a rod-only retina. To explore role signaling molecules modulating function, we identified putative sites post-translational modification protein by silico analysis. Here, demonstrate...
Abstract Retinal progenitor cells (RPCs) are the source of all retinal cell types during retinogenesis. Until now, isolation and expansion RPCs has been at expense their multipotency. Here, we report simple methods media for generation, expansion, cryopreservation human induced pluripotent stem-cell derived-RPCs (hiRPCs). Thawed passed hiRPCs maintained biochemical transcriptional RPC phenotypes ability to differentiate into types. Specific conditions allowed generation large cultures...
In the mammalian retina, rod and cone photoreceptors transmit visual information to bipolar neurons through highly specialized ribbon synapses. We have limited understanding of regulatory pathways that guide morphogenesis organization photoreceptor presynaptic architecture in developing retina. While neural retina leucine zipper (NRL) transcription factor determines cell fate function, cone-rod homeobox (CRX) controls expression both rod- cone-specific genes is critical for terminal...
Abstract Muller glial cells (MGCs) are responsible for the homeostatic and metabolic support of retina. Despite importance MGCs in retinal disorders, reliable accessible human cell sources to be used model MGC‐associated diseases lacking. Although primary (pMGCs) can purified from post‐mortem tissues, donor scarcity limits their use. To overcome this problem, we developed a protocol generate bank induced pluripotent stem cell‐derived (hiMGCs). Using transcriptome analysis, showed that three...
In multicellular eukaryotic organisms, the initiation of DNA replication occurs asynchronously throughout S-phase according to a regulated timing program. Here, using Xenopus egg extracts, we showed that Yap (Yes-associated protein 1), downstream effector Hippo signalling pathway, is required for control dynamics. We found recruited chromatin at start and identified Rif1, major regulator program, as novel binding protein. Furthermore, show either or Rif1 depletion accelerates dynamics by...
Hippo signalling regulates eye growth during embryogenesis through its effectors YAP and TAZ. Taking advantage of a Yap heterozygous mouse line, we here sought to examine function in adult neural retina, where expression is restricted Müller glia. We first discovered an unexpected temporal dynamic gene compensation. At postnatal stages, Taz upregulation occurs, leading gain function-like phenotype characterised by EGFR potentiation delayed cell-cycle exit retinal progenitors. In contrast,...