A5045505796- MicroRNA in disease regulation
- Neurogenesis and neuroplasticity mechanisms
- RNA Research and Splicing
- Chromatin Remodeling and Cancer
- Cancer-related molecular mechanisms research
- Congenital heart defects research
- Pluripotent Stem Cells Research
- Genetics and Neurodevelopmental Disorders
- RNA regulation and disease
- Epigenetics and DNA Methylation
- Signaling Pathways in Disease
- Hereditary Neurological Disorders
- Nerve injury and regeneration
- Hedgehog Signaling Pathway Studies
- Nuclear Receptors and Signaling
- Tumors and Oncological Cases
- Peroxisome Proliferator-Activated Receptors
- Biofuel production and bioconversion
- Developmental Biology and Gene Regulation
- Enzyme Catalysis and Immobilization
- FOXO transcription factor regulation
- Microbial Metabolic Engineering and Bioproduction
- Neurogenetic and Muscular Disorders Research
- Circular RNAs in diseases
- Genomics and Chromatin Dynamics
Friedrich-Alexander-Universität Erlangen-Nürnberg
2012-2024
Fischer (Germany)
2019
The HMG-domain transcription factor Sox10 is expressed throughout oligodendrocyte development and an important component of the transcriptional regulatory network in these myelin-forming CNS glia. Of known regions, only evolutionary conserved U2 enhancer distal 5′-flank gene exhibits oligodendroglial activity. We found that was active precursors, but not mature oligodendrocytes. activity also did mediate initial induction after specification arguing expression during depends on multiple...
Neural precursor cells of the ventricular zone give rise to all neurons and glia central nervous system rely for maintenance their characteristics on closely related SoxB1 transcription factors Sox1, Sox2 Sox3. We show in mouse spinal cord that, whereas proteins are usually downregulated upon neuronal specification, they continue be expressed glial precursors. In oligodendrocyte lineage, Sox3 remain present into early phases terminal differentiation. Surprisingly, deletion does not alter but...
Oligodendrocytes produce myelin for rapid transmission and saltatory conduction of action potentials in the vertebrate central nervous system. Activation myelination program requires several transcription factors including Sox10, Olig2, Nkx2.2. Functional interactions among them are poorly understood important components regulatory network still unknown. Here, we identify Nfat proteins as Sox10 targets regulators oligodendroglial differentiation rodents humans. Overall levels nuclear...
Myelinating Schwann cells in the vertebrate peripheral nervous system rely on Brg1 (Smarca4) for terminal differentiation. serves as central ATP-hydrolyzing subunit of chromatin remodelling BAF complexes and is recruited during myelination part these by transcription factor Sox10 cells. Here, we analyzed role development myelinating oligodendrocytes CNS mouse. Following deletion oligodendrocyte precursors, showed normal survival, proliferation, migration. A mild but significant reduction...
Several transcription factors are essential for terminal differentiation of myelinating glia, among them the high-mobility-group-domain-containing protein Sox10. To better understand how these exert their effects and shape glial expression programs, we identified characterized a physical functional link between Sox10 Med12 subunit Mediator complex that serves as conserved multiprotein interphase general machinery. We found bound with two its domains to C-terminal region close relative,...
During development of myelin-forming oligodendrocytes in the central nervous system two closely related transcription factors Sox9 and Sox10 play essential roles that are partly shared unique. Whereas primarily functions during oligodendroglial specification, is uniquely required to induce terminal differentiation myelination. this process, protein levels rise substantially. As coincides with a reciprocal decrease Sox9, we postulated influences amounts differentiating oligodendrocytes. Here...
Oligodendrocytes are the myelinating glia of central nervous system and ensure rapid saltatory conduction. Shortage or loss these cells leads to severe malfunctions as observed in human leukodystrophies multiple sclerosis, their replenishment by reprogramming cell conversion strategies is an important research aim. Using a transgenic approach we increased levels transcription factor Sox10 throughout mouse embryo thereby prompted Fabp7-positive glial dorsal root ganglia peripheral convert...
Abstract Differentiating oligodendrocytes generate myelin to ensure rapid saltatory conduction in the vertebrate central nervous system. Although oligodendroglial differentiation and myelination are accompanied by dramatic chromatin reorganizations, previously studied remodelers had only limited direct effects on process. To study functional significance of changes for identify relevant remodelers, we deleted Ep400, ATP-hydrolyzing subunit TIP60/EP400 complex, at defined times mouse...
Differentiation of oligodendrocytes and myelin production in the vertebrate central nervous system require highly concerted changes gene expression. The transcription factors Sox10 Myrf are both to this process jointly regulate expression genes. Here we show that also cooperate activation coding for dual specificity protein phosphatase Dusp15 (also known as VHY) during process. Activation is mediated by promoter, which sufficient drive oligodendroglial vivo. It contains a functional binding...
Abstract The high‐mobility‐group domain‐containing transcription factor Sox9 confers glial competence to neuroepithelial precursors in the developing central nervous system and is an important determinant of astroglial oligodendroglial specification. In cells, it remains expressed oligodendrocyte progenitor cells (OPCs) system, but shut off differentiating oligodendrocytes as well OPCs that persist adult system. To better understand role OPCs, we generated mouse models allowed expression a...
Schwann cells are the main glial cell type in PNS. They develop along nerves during embryogenesis and rely on HMG domain containing Sox10 transcription factor for specification, lineage progression, terminal differentiation. deletion immature caused peripheral nerve defects mice that were not restricted to this type, although expression gene loss were. Formation of perineurium as protecting sheath was, instance, heavily compromised. This resembled defect observed after Desert hedgehog (Dhh)...
ABSTRACT Corynebacterium glutamicum has two different Amt-type proteins. While AmtB a low substrate affinity and is not saturable up to 3 mM methylammonium, AmtA high mediates saturable, membrane potential-dependent transport, resulting in steady-state accumulation of even the absence metabolic trapping.
Congenital hypomyelinating neuropathy (CHN) is a rare congenital that presents in the neonatal period and has been linked previously to mutations several genes associated with myelination. A recent study 4 homozygous frameshift contactin-associated protein 1 (CNTNAP1) gene this condition.We report neonate CHN who was found have absent sensory nerve compound muscle action potentials hypomyelination on biopsy.On whole exome sequencing, we identified novel CNTNAP1 missense mutation...
Abstract In oligodendrocytes of the vertebrate central nervous system a complex network transcriptional regulators is required to ensure correct and timely myelination neuronal axons. Here we identify Zfp276, only mammalian ZAD-domain containing zinc finger protein, as regulator oligodendrocyte differentiation downstream Sox10. system, Zfp276 exclusively expressed in mature oligodendrocytes. Oligodendroglial deletion led strongly reduced expression myelin genes early postnatal mouse spinal...
The transcription factor Sox10 is an important determinant of oligodendroglial identity and influences development characteristics at various stages. Starting from RNA-seq data, we here show that the expression several voltage-gated ion channels with known function in cells depends upon Sox10. These include Nav1.1, Cav2.2, Kv1.1, Kir4.1 channels. For each four encoding genes, found least one regulatory region activated by vitro same time bound vivo. Cell-specific deletion furthermore led to...
Oligodendrocytes and Schwann cells are the myelinating glia of vertebrate nervous system by generation myelin sheaths allow rapid saltatory conduction. Previous in vitro work had pointed to a role zinc finger containing specificity proteins Sp1 Sp3 as major regulators glial differentiation myelination. Here, we asked whether such is also evident vivo using mice with specific deletions or glia. We studied glia-specific conditional Sp2- constitutive Sp4-deficient include all related...
The high-mobility-group domain containing SoxC transcription factors Sox4 and Sox11 are expressed required in the vertebrate central nervous system neuronal precursors neuroblasts. To identify genes that widely regulated by proteins during neurogenesis we generated expression profiles from developing mouse brain chicken neural tube with reduced found factor prospero homeobox protein 1 (Prox1) strongly down-regulated under both conditions. This led us to hypothesize Prox1 depends on of...
The HMG-domain containing transcription factor Sox10 plays a crucial role in regulating Schwann cell survival and differentiation is expressed throughout the entire lineage. While its importance peripheral myelination well established, little known about early stages of development. In search for direct target genes precursors, transcriptional co-repressor Tle4 was identified. At least two regions upstream gene appear involved mediating Sox10-dependent activation. Once induced, works tandem...