RNA expression in mutants of the miRNA pathway during myelination
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE64880 | GEO | 2018/10/08
REPOSITORIES: GEO
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Project description:We addressed the requirement of DGCR8, DROSHA and DICER functions in developing and adult Schwann cells (SCs) using mouse mutants. We found that the microprocessor components DGCR8 and DROSHA are crucial for axonal radial sorting and to establish correct SC numbers upon myelination. Transcriptome analysis revealed that the microprocessor is essential to prevent aberrant accumulation and de novo expression of injury-response genes. Those genes are predicted targets of stage-specifically enriched miRNAs. In agreement, DGCR8 and DICER are required for proper maintenance of the myelinated SC state. We conclude that the miRNA pathway is crucial for preventing inappropriate activity of injury response genes in developing and adult SCs.
2018-10-08 | GSE109075 | 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:To address the role of monoubiquitination of histone H2B at lysine 120 (H2Bub1), we inactivated the responsible E3 ligase by deleting Rnf40 in developing Schwann cells. Rnf40 becomes important for proper Schwann cell development shortly before and during differentiation. Its absence in Schwann cells leads to a peripheral neuropathy. RNA-Seq studies were performed on sciatic nerves from control mice and mice with a Schwann cell-specific deletion of Rnf40 to analyze changes in gene expression. These revealed substantial changes in the expression of genes associated with myelination, lipid metabolism and cell adhesion.
2020-07-13 | GSE146629 | GEO
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:To address the role of monoubiquitination of histone H2B at lysine 120 (H2Bub1), we inactivated the responsible E3 ligase by deleting Rnf40 in developing Schwann cells. Rnf40 becomes important for proper Schwann cell development shortly before and during differentiation. Its absence in Schwann cells leads to a peripheral neuropathy. ChIP-Seq studies with H2Bub1-specific antibodies were performed on sciatic nerves from control mice and mice with a Schwann cell-specific deletion of Rnf40 to detect alterations in genomic H2Bub1 occupancy. These correlated with changes in the expression of genes associated with myelination and lipid metabolism.
2020-07-13 | GSE146645 | GEO
Project description:Schwann cell maturation is tightly controlled by a set of transcriptional regulators. We have deleted the zinc-finger transcription factor Sip1 specifically from immature Schwann cells and observed a dramatic developmental delay. In an attempt to define the developmental stage of Sip1-deficient Schwann cells, we performed microarray analysis of Schwann cell-specific mutants compared to controls at the age of 25 days (P25). Sciatic nerves of 3 mutant mice and 3 corresponding controls were isolated at the age of 25 days.
2016-06-13 | E-GEOD-76027 | biostudies-arrayexpress
Project description:We report RNA sequencing data from induced Schwann cell specific knockouts for DICER and DGCR8 as well as crush injured wild type animals. Induced deletion of DICER and DGCR8 results in expression of numerous injury response genes suggesting a requirement of those proteins in maintaining the myelinated Schwann cell fate.
2018-10-08 | GSE109074 | GEO
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:Analysis of gene expression in LKB1(Stk11)-depleted sciatic nerves (LKB1-SCKO) vs control nerves from age-matched mice. Gene expression profiles are predominantly derived from Schwann cell glia and provide important information about the response of peripheral nerve Schwann cells to inactivation of the metabolic regulator protein LKB1(aka Stk11). Total RNA obtained from sciatic nerve segments from 6 LKB1-SCKO mutant mice compared to RNA from nerve segments from 6 control mice (floxed LKB1 mutant mice that do not express Cre recombinase).
2014-08-12 | E-GEOD-60325 | biostudies-arrayexpress
Project description:Analysis of gene expression in LKB1(Stk11)-depleted sciatic nerves (LKB1-SCKO) vs control nerves from age-matched mice. Gene expression profiles are predominantly derived from Schwann cell glia and provide important information about the response of peripheral nerve Schwann cells to inactivation of the metabolic regulator protein LKB1(aka Stk11).
2014-08-12 | GSE60325 | GEO