Expression Profile Analysis of Rat Motoneurons During Myelination
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE133744 | GEO | 2020/07/09
REPOSITORIES: GEO
Similar Datasets
Project description:The myelin sheaths that surround the thick axons of the peripheral nervous system are produced by the highly specialized Schwann cells. Differentiation of Schwann cells and myelination occur in discrete steps. Each of these requires coordinated expression of specific proteins in a precise sequence, yet the regulatory mechanisms controlling protein expression during these events are incompletely understood. Here we report that Schwann cell-specific ablation of the enzyme Dicer1, which is required for the production of small non-coding regulatory microRNAs, fully arrests Schwann cell differentiation, resulting in early postnatal lethality. Dicer-/- Schwann cells had lost their ability to myelinate, yet were still capable of sorting axons. Both cell death and, paradoxically, proliferation of immature Schwann cells was vastly enhanced, suggesting that their terminal differentiation is triggered by growth-arresting regulatory microRNAs. Using microRNA microarrays, we identified 16 miRNAs that are upregulated upon myelination and whose expression is controlled by Dicer in Schwann cells. This set of microRNAs appears to drive Schwann cell differentiation and myelination of peripheral nerves, thereby fulfilling a crucial function for survival of the organism. Samples representing Schwann cell-specific ablation of the enzyme Dicer1 and wild type controls at developmental stages E17 and P4. Geometric mean-averaged data linked below as supplementary file.
2010-12-01 | E-GEOD-22023 | biostudies-arrayexpress
Project description:Chromatin organization is critical for cell growth, differentiation, and disease development, however, its functions in peripheral myelination and myelin repair remain elusive. Here we observed a global diminution of chromatin accessibility during Schwann cell differentiation and demonstrated that the chromatin organizer CCCTC-binding factor (CTCF) is critical for Schwann cell myelination and myelin regeneration after nerve injury. Inhibition of Ctcf or its deletion blocked Schwann cell differentiation at the pre-myelinating stage, whereas overexpression of CTCF promoted the myelination program. CTCF establishes the chromatin interaction loop between promoters and regulatory elements to promote expression of key pro-myelinogenic factors such as EGR2. In addition, CTCF interacts with SUZ12, a component of polycomb-repressive-complex 2, to repress expression of immature Schwann cell-associated regulators including HES1, RSPO2, and CALCA. Together, our findings reveal the dual role of CTCF-dependent chromatin organization in promoting myelinogenic programs and recruiting chromatin-repressive complexes to block differentiation inhibitors to control peripheral myelination and myelin repair.
2020-06-22 | GSE138117 | GEO
Project description:Expression Profile Analysis of Rat Motoneurons During Myelination
| PRJNA552365 | ENA
Project description:The myelin sheaths that surround the thick axons of the peripheral nervous system are produced by the highly specialized Schwann cells. Differentiation of Schwann cells and myelination occur in discrete steps. Each of these requires coordinated expression of specific proteins in a precise sequence, yet the regulatory mechanisms controlling protein expression during these events are incompletely understood. Here we report that Schwann cell-specific ablation of the enzyme Dicer1, which is required for the production of small non-coding regulatory microRNAs, fully arrests Schwann cell differentiation, resulting in early postnatal lethality. Dicer-/- Schwann cells had lost their ability to myelinate, yet were still capable of sorting axons. Both cell death and, paradoxically, proliferation of immature Schwann cells was vastly enhanced, suggesting that their terminal differentiation is triggered by growth-arresting regulatory microRNAs. Using microRNA microarrays, we identified 16 miRNAs that are upregulated upon myelination and whose expression is controlled by Dicer in Schwann cells. This set of microRNAs appears to drive Schwann cell differentiation and myelination of peripheral nerves, thereby fulfilling a crucial function for survival of the organism.
2010-12-01 | GSE22023 | GEO
Project description:Myelination is essential for nervous system function. Schwann cells interact with neurons and with the basal lamina to sort and myelinate axons, using known receptors and signaling pathways. In contrast, the transcriptional control of axonal sorting and the role of mechano-transduction in myelination are largely unknown. Yap and Taz are effectors of the Hippo pathway that integrate chemical and mechanical signals in cells. Here, we describe a previously unknown role for the Hippo pathway in myelination. Using conditional mutagenesis in mice we show that Taz is required in Schwann cells for radial sorting and myelination. Yap is redundant with Taz as ablation of both Yap and Taz abolishes radial sorting. Yap/Taz regulate Schwann cell proliferation and transcription of basal lamina receptors, both necessary for proper radial sorting of axons, and subsequent myelination. These data link transcriptional effectors of the Hippo pathway and of mechanotransduction to myelin formation in Schwann cells.
2016-06-06 | GSE79115 | GEO
Project description:The aim of our study is to determine the functions of histone deacetylases (HDACs) 1 and 2 in Schwann cells during postnatal development of the peripheral nervous system (PNS). Schwann cells are the myelinating glial cells of the PNS. At birth, mouse sciatic nerves mature in 2 subsequent phases: 1/ big caliber axons get sorted into a 1 to 1 relationship with Schwann cells, 2/ Schwann cells build a myelin sheath around sorted axons. In mice where both HDAC1 & HDAC2 have been specifically knocked out in Schwann cells, both phases are impaired. HDACs are chromatin remodeling enzymes, they can thus alter gene expression directly. We want to identify which genes controlled by HDAC1 and HDAC2 in Schwann cells are necessary for the maturation of sciatic nerves. Because HDAC1 and HDAC2 can compensate for each other loss to some extend, we will first analyze changes of gene expression in HDAC1/HDAC2 double KO animals. We expect to gain critical insights into the molecular mechanisms controlling Schwann cell differentiation and myelination. This knowledge is of key importance for the success of regenerative medicine in peripheral neuropathies, nerve tumors, and transplantation paradigms in non-regenerative CNS lesions and in large PNS injuries. 3 double knockout mutants for HDAC1 and HDAC2 and 3 control littermates were analyzed. Tissues analyzed: sciatic nerves of 2 day-old mouse pups
2011-02-25 | E-GEOD-27451 | biostudies-arrayexpress
Project description:Axonal myelination is essential for neuronal function and health. In peripheral nerves, deficient myelination is responsible for the morbidity of various forms of inherited or acquired neuropathies, including Charcot-Marie-Tooth disease and diabetic neuropathy. Decades of research have uncovered a complex transcriptional and post-transcriptional program that co-ordinates the formation and maintenance of the myelin sheath. In contrast, much less is known about the functional role of post-translational modification (PTM) of proteins in this remarkable biogenic process. Neddylation, a PTM that involves the conjugation of the ubiquitin-like protein Nedd8 to protein targets, has recently emerged as a central and versatile regulator of many cellular processes, including gene transcription, metabolism, and cellular differentiation. In this study, we show that genetic and pharmacological inhibition of neddylation in vivo in developing Schwann cells lead to striking nerve defects that exhibit the classical hallmarks of a severe neuropathy, including gait abnormalities, muscle weakness, and hindlimb clasping, ultimately leading to early death. The mutant mice lack peripheral myelin and develop secondary axonal loss, and we demonstrate, at the mechanistic level, that neddylation regulates multiple critical myelination-related pathways. Together, our findings identify neddylation as a central regulatory hub of control of peripheral myelination and delineate the potential pathogenetic mechanisms in inherited human PNS disorders, characterized by mutations in genes related to the neddylation pathway.
2024-06-16 | PXD043917 | Pride
Project description:Schwann cell remyelination defects impair functional restoration after nerve damage, contributing to peripheral neuropathies. The mechanisms that mediate remyelination block remain elusive. Upon small-molecule epigenetic screening, we identified HDAC3, a histone-modifying enzyme, as a potent inhibitor of peripheral myelinogenesis. Inhibition of HDAC3 markedly enhances myelin growth and regeneration, and improves functional recovery after peripheral nerve injury. HDAC3 antagonizes myelinogenic neuregulin/PI3K/AKT signaling axis. Moreover, genome-wide profiling analyses reveal that HDAC3 represses pro-myelinating programs through epigenetic silencing, while coordinating with p300 histone acetyltransferase to activate myelination-inhibitory programs that include HIPPO signaling effector TEAD4 to inhibit myelin growth. Schwann-cell-specific deletion of either Hdac3 or Tead4 results in a profound increase in myelin thickness in sciatic nerves. Thus, our findings identify the HDAC3-TEAD4 network as a dual-function switch of cell-intrinsic inhibitory machinery that counters myelinogenic signals and maintains peripheral myelin homeostasis, highlighting the therapeutic potential of transient HDAC3 inhibition for improving peripheral myelin repair.
2018-02-11 | GSE93160 | GEO
Project description:Schwann cell remyelination defects impair functional restoration after nerve damage, contributing to peripheral neuropathies. The mechanisms that mediate remyelination block remain elusive. Upon small-molecule epigenetic screening, we identified HDAC3, a histone-modifying enzyme, as a potent inhibitor of peripheral myelinogenesis. Inhibition of HDAC3 markedly enhances myelin growth and regeneration, and improves functional recovery after peripheral nerve injury. HDAC3 antagonizes myelinogenic neuregulin/PI3K/AKT signaling axis. Moreover, genome-wide profiling analyses reveal that HDAC3 represses pro-myelinating programs through epigenetic silencing, while coordinating with p300 histone acetyltransferase to activate myelination-inhibitory programs that include HIPPO signaling effector TEAD4 to inhibit myelin growth. Schwann-cell-specific deletion of either Hdac3 or Tead4 results in a profound increase in myelin thickness in sciatic nerves. Thus, our findings identify the HDAC3-TEAD4 network as a dual-function switch of cell-intrinsic inhibitory machinery that counters myelinogenic signals and maintains peripheral myelin homeostasis, highlighting the therapeutic potential of transient HDAC3 inhibition for improving peripheral myelin repair.
2018-02-11 | GSE93159 | GEO
Project description:To determine spinal cord injury (SCI) induced changes in gene expression, laser capture microscopy (LCM) and Affymetrix microarrays were used to profiles three distinct populations of motor neurons (MNs) in five sets of littermates. In each set, one littermate received a lamenectomy (sham operated), and the other received a complete spinal cord transection. Each MN population was caudal to the transection and not axotomized. Thus, MNs in transected animals were responding to two major insults: deafferentation and changing microenvironments due to spreading immune and inflammatory responses. A total of 30 expression profiles from sham operated control animals have been uploaded to GEO database with accession number GSE2595. The current series contains 32 motoneuron expression profiles from spinalized mice. All chips (30 sham + 32 transection) were generated together using RMA in 2004. Experiment Overall Design: In this study we determine SCI induced changes in gene expression in lateral motoneurons (LMN), medial motoneurons (MMN) and intermediolateral column motoneurons (IML). Five sets of male littermates were used in these experiments (sets a-e). In each set, one littermate received a lamenectomy (sham operated), and the other received a complete spinal cord transection. Four of the sets (a-d) consisted of one transect and one littermate sham operated control. The fifth set (e) had an additional transect. All surgeries were performed on postnatal day (P) 24. Three weeks later (P45), the animals were sacrificed and their spinal cords were removed and sectioned for LCM. Each of the three cell types was captured from every animal. The expression profiles of the three classes of MNs were obtained using Affymetrix microarrays.
2009-09-25 | E-GEOD-18179 | biostudies-arrayexpress