Ddx20, DEAD box helicase 20, is essential for the differentiation of oligodendrocyte and maintenance of myelin gene expression.


Journal

Glia
ISSN: 1098-1136
Titre abrégé: Glia
Pays: United States
ID NLM: 8806785

Informations de publication

Date de publication:
11 2021
Historique:
revised: 24 06 2021
received: 17 03 2021
accepted: 25 06 2021
pubmed: 8 7 2021
medline: 12 3 2022
entrez: 7 7 2021
Statut: ppublish

Résumé

Oligodendrocytes form myelin sheaths that surround axons, contributing to saltatory conduction and proper central nervous system (CNS) function. Oligodendrocyte progenitor cells (OPCs) are generated during the embryonic stage and differentiate into myelinating oligodendrocytes postnatally. Ddx20 is a multifunctional, DEAD-box helicase involved in multiple cellular processes, including transcription, splicing, microRNA biogenesis, and translation. Although defects in each of these processes result in abnormal oligodendrocyte differentiation and myelination, the involvement of Ddx20 in oligodendrocyte terminal differentiation remains unknown. To address this question, we used Mbp-Cre mice to generate Ddx20 conditional knockout (cKO) mice to allow for the deletion of Ddx20 from mature oligodendrocytes. Mbp-Cre;Ddx20 cKO mice demonstrated small body sizes, behavioral abnormalities, muscle weakness, and short lifespans, with mortality by the age of 2 months old. Histological analyses demonstrated significant reductions in the number of mature oligodendrocytes and drastic reductions in the expression levels of myelin-associated mRNAs, such as Mbp and Plp at postnatal day 42. The number of OPCs did not change. A thin myelin layer was observed for large-diameter axons in Ddx20 cKO mice, based on electron microscopic analysis. A bromodeoxyuridine (BrdU) labeling experiment demonstrated that terminal differentiation was perturbed from ages 2 weeks to 7 weeks in the CNS of Mbp-Cre;Ddx20 cKO mice. The activation of mitogen-activated protein (MAP) kinase, which promotes myelination, was downregulated in the Ddx20 cKO mice based on immunohistochemical detection. These results indicate that Ddx20 is an essential factor for terminal differentiation of oligodendrocytes and maintenance of myelin gene expression.

Identifiants

pubmed: 34231259
doi: 10.1002/glia.24058
doi:

Substances chimiques

DEAD Box Protein 20 EC 3.6.1.-
Ddx20 protein, mouse EC 3.6.1.-
DEAD-box RNA Helicases EC 3.6.4.13

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2559-2574

Informations de copyright

© 2021 Wiley Periodicals LLC.

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Auteurs

Anna Simankova (A)

Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

Norihisa Bizen (N)

Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

Sei Saitoh (S)

Section of Electron Microscopy, Supportive Center for Brain Research, National Institute for Physiological Sciences, Okazaki, Japan.
Department of Biomedical Molecular Sciences (Anatomy II), Fujita Health University School of Medicine, Toyoake, Japan.

Shinsuke Shibata (S)

Division of Microscopic Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.

Nobuhiko Ohno (N)

Department of Anatomy, Division of Histology and Cell Biology, School of Medicine, Jichi Medical University, Shimotsuke, Japan.
Division of Ultrastructural Research, National Institute for Physiological Sciences, Okazaki, Japan.

Manabu Abe (M)

Department of Animal Model Development, Brain Research Institute, Niigata University, Niigata, Japan.

Kenji Sakimura (K)

Department of Animal Model Development, Brain Research Institute, Niigata University, Niigata, Japan.

Hirohide Takebayashi (H)

Division of Neurobiology and Anatomy, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Center for Coordination of Research Facilities, Niigata University, Niigata, Japan.

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