Ablation of Dicer from Murine Schwann Cells Increases Their Proliferation while Blocking Myelination
Open accessAbstract
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 markedly enhanced, suggesting that their terminal differentiation is triggered by growth-arresting regulatory microRNAs. Using microRNA microarrays, we identified 16 microRNAs 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.
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Autophagy is regulated by distinct mechanisms in different cell types, and these cell type-specific mechanisms underlie the differential vulnerability of separate tissues to autophagy mutations, resulting in heterogeneous manifestations of disease.
“Furthermore, mounting evidence shows that autophagy is regulated by distinct mechanisms in different cell types [11–26], and these cell type-specific mechanisms underlie the differential vulnerability of separate tissues to autophagy mutations, resulting in heterogenous manifestations of disease.”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [14]
Remyelination after peripheral nerve injury is hindered by injury-induced upregulation of microRNA Mir195a, which inhibits Atg14 and suppresses Schwann cell autophagy.
“Remyelination after peripheral nerve injury is hindered by injury-induced upregulation of the microRNA Mir195a, which inhibits Atg14 and, in turn, suppresses Schwann cell autophagy [14,15].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [14]
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“Schwann cells Activates [465] Activates [467,468] FIG4 [13] MIR195 [14,15]”
Background
- Authors
- Bremer, J., O'Connor, T., Tiberi, C., Rehrauer, H., Weis, J., & Aguzzi, A.
- Affiliations
- University Hospital Zurich (CH)
- University of Zurich (CH)
- RWTH Aachen University (DE)
- Corresponding author
- Aguzzi, Adriano
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-08-27
- Volume
- 5
- Issue
- 8
- Pages
- e12450
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2929198
- OpenAlex
- W2039405357
- Cited by
- 87
- References
- 33
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 3 · 2023: 3 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 2 · 2016: 4 · 2015: 11 · 2014: 8 · 2013: 4 · 2012: 9
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- RWTH Publications (RWTH Aachen) (submittedVersion, cc-by)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
- RWTH Publications (RWTH Aachen)
- ETH Zürich Research Collection (cc-by)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Novartis Foundation
- European Commission
- Universität Zürich
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- DICER1, Schwann cells, myelination, Schwann cell differentiation, microRNA, Schwann cell proliferation, axon sorting, postnatal lethality, peripheral nervous system, miRNA microarray
- MeSH terms
- Animals, Endoribonucleases, Gene Expression Regulation, Myelin Sheath, Schwann Cells, Signal Transduction, Gene Deletion, MicroRNAs, Ribonuclease III, Cell Proliferation, Mice, DEAD-box RNA Helicases
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