A5069986045- Developmental Biology and Gene Regulation
- Muscle Physiology and Disorders
- RNA Research and Splicing
- Invertebrate Immune Response Mechanisms
- Chromosomal and Genetic Variations
- Cardiomyopathy and Myosin Studies
- Ubiquitin and proteasome pathways
- Neurobiology and Insect Physiology Research
- Peptidase Inhibition and Analysis
- Congenital heart defects research
- Animal Genetics and Reproduction
- Signaling Pathways in Disease
- Genetic Neurodegenerative Diseases
- Nuclear Structure and Function
- Genomics and Rare Diseases
- Insect and Arachnid Ecology and Behavior
- Genomics and Chromatin Dynamics
- Mitochondrial Function and Pathology
- Genetics, Aging, and Longevity in Model Organisms
- RNA modifications and cancer
- Metabolism and Genetic Disorders
- Ion channel regulation and function
- Neurogenetic and Muscular Disorders Research
- ATP Synthase and ATPases Research
- Calpain Protease Function and Regulation
Institut de génétique et de développement de Rennes
2021-2024
Centre de Biologie du Développement
2010-2024
Centre National de la Recherche Scientifique
2010-2024
Université de Rennes
2021-2024
University of Cambridge
2014-2020
Université de Toulouse
2012-2017
Université Toulouse III - Paul Sabatier
2010-2017
Sorbonne Université
2014
Abstract Most eukaryotic proteins are N-terminally acetylated, but the functional impact on a global scale has remained obscure. Using genome-wide CRISPR knockout screens in human cells, we reveal strong genetic dependency between major N-terminal acetyltransferase and specific ubiquitin ligases. Biochemical analyses uncover that both ligase complex UBR4-KCMF1 NatC recognize bearing an unacetylated methionine followed by hydrophobic residue. KO-induced protein degradation phenotypes reversed...
Adult stem cells are important for tissue maintenance and repair. One key question is how such specified then protected from differentiation a prolonged period. Investigating the of Drosophila muscle progenitors (MPs) we demonstrate that it involves switch in zfh1/ZEB1 RNA-isoforms. Differentiation into functional muscles accompanied by expression miR-8/miR-200, which targets major zfh1-long RNA isoform decreases Zfh1 protein. Through activity Notch pathway, subset MPs produce an alternate...
Hox transcription factors control many aspects of animal morphogenetic diversity. The segmental pattern Drosophila larval muscles shows stereotyped variations along the anteroposterior body axis. Each muscle is seeded by a founder cell and properties specific to each reflect expression combination 'identity' factors. Founder cells originate from asymmetric division progenitor specified at fixed positions. Using dorsal DA3 lineage as paradigm, we show here that proteins play decisive role in...
The LIM-homeodomain transcription factor Tailup/Islet1 (Tup) is a key component of cardiogenesis in Drosophila and vertebrates. We report here an additional major role for Tup specifying dorsal muscles. expressed the four muscle progenitors (PCs) tup-null embryos display severely disorganized musculature, including transformation DA2 into dorsolateral DA3 muscle. This reciprocal to observed collier (col) mutants. PC, which gives rise adult precursor, selected from cluster myoblasts...
The T-box transcription factor Tbx1 and the LIM-homeodomain Islet1 are key components in regulatory circuits that generate myogenic cardiogenic lineage diversity chordates. We show here Org-1 Tup, Drosophila orthologs of Islet1, co-expressed required for formation heart-associated alary muscles (AMs) abdomen. same holds true lineage-related thorax have not been described previously, which we name thoracic alary-related (TARMs). Lineage analyses identified progenitor cell each AM TARM....
A stereotyped array of body wall muscles enables precision and stereotypy animal movements. In Drosophila, each syncytial muscle forms via fusion one founder cell (FC) with multiple competent myoblasts (FCMs). The specific morphology muscle, i.e. distinctive shape, orientation, size skeletal attachment sites, reflects the combination identity transcription factors (iTFs) expressed by its FC. Here, we addressed three questions: Are FCM nuclei naive? What is selectivity temporal sequence...
There is growing evidence that Notch pathway activation can result in consequences on cell morphogenesis and behaviour, both during embryonic development cancer progression. In general, proposed to co-ordinate these processes by regulating expression of key transcription factors. However, many Notch-regulated genes identified genome-wide studies are involved fundamental aspects suggesting a more direct influence cellular properties. By testing the functions 25 such we confirmed 12 required...
SUMMARY Most eukaryotic proteins are N-terminally acetylated, but the functional impact on a global scale has remained obscure. Using genome-wide CRISPR knockout screens in human cells, we reveal strong genetic dependency between major N-terminal acetyltransferase and specific ubiquitin ligases. Biochemical analyses uncover that both ligase complex UBR4-KCMF1 NatC recognize bearing an unacetylated methionine followed by hydrophobic residue. KO-induced protein degradation phenotypes reversed...
Mitochondrial disorders associated with genetic defects of the ATP synthase are among most deleterious diseases neuromuscular system that primarily manifest in newborns. Nevertheless, number established animal models for elucidation molecular mechanisms behind such pathologies is limited. In this paper, we target Drosophila melanogaster gene encoding subunit c, ATPsynC, order to create a fruit fly model investigating mitochondrial bioenergetics and better understand comprehensive...
The underlying mechanisms for statin-induced myopathy (SIM) are still equivocal. In this study, we employ Drosophila melanogaster to dissect possible SIM. We observe that chronic fluvastatin treatment causes reduced general locomotion activity and climbing ability. addition, transmission microscopy of dissected skeletal muscles fluvastatin-treated flies reveals strong myofibrillar damage, including increased sarcomere lengths Z-line streaming, which reminiscent myopathy, along with...
Abstract Previously, we showed that fluvastatin treatment induces myofibrillar damage and mitochondrial phenotypes in the skeletal muscles of Drosophila . However, sequential occurrence myofibril remains elusive. To address this, treated flies with for two five days examined their thorax flight using confocal microscopy. In two-day group, compared to control, exhibited morphological changes, including fragmentation, rounding up reduced content, while myofibrils remained organized parallel....
Skeletal muscles are large syncytia made up of many bundled myofibers that produce forces and enable body motion. Drosophila is a classical model to study muscle biology. The combination both genetics advanced omics approaches led the identification key conserved molecules regulate morphogenesis regeneration. However, transcriptional dynamics these spatial distribution their messenger RNA within cannot be assessed by conventional methods. Here we optimized an existing single-molecule...
There is growing evidence that Notch pathway activation can result in consequences on cell morphogenesis and behaviour, both during embryonic development cancer progression.In general, proposed to co-ordinate these processes by regulating expression of key transcription factors.However, many Notch-regulated genes identified genome-wide studies are involved fundamental aspects suggesting a more direct influence cellular properties.By testing the functions 25 such we confirmed 12 required...
Skeletal muscles are large syncytia made up of many bundled myofibers that produce forces and enable body motion. Drosophila is a classical model to study muscle biology. The combination both genetics advanced omics approaches led the identification key conserved molecules regulate morphogenesis regeneration. However, transcriptional dynamics these spatial distribution their messenger RNA within cannot be assessed by conventional methods. Here we optimized an existing single-molecule...
Summary Adult stem cells are important for tissue maintenance and repair. One key question is how such specified then protected from differentiation a prolonged period. Investigating the of Drosophila muscle progenitors (MPs) we demonstrate that it involves switch in zfh1/ZEB1 RNA-isoforms. Differentiation into functional muscles accompanied by expression miR - 8/miR 200 , which targets major zfh1 long RNA isoform decreases Zfh1 protein. Through activity Notch pathway, subset MPs produce an...