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PMID: 12456652 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Normal timing of oligodendrocyte development depends on thyroid hormone receptor alpha 1 (TRalpha1).

The EMBO journal ·Vol. 21 ·No. 23 ·2002-12-02 ·Pages 6452-60

Billon N, Jolicoeur C, Tokumoto Y, Vennström B, Raff M

Abstract

The timing of oligodendrocyte development is regulated by thyroid hormone (TH) in vitro and in vivo, but it is still uncertain which TH receptors mediate this regulation. TH acts through nuclear receptors that are encoded by two genes, TRalpha and TRbeta. Here, we provide direct evidence for the involvement of the TRalpha1 receptor isoform in vivo, by showing that the number of oligodendrocytes in the postnatal day 7 (P7) and P14 optic nerve of TRalpha1-/- mice is decreased compared with normal. We demonstrate that TRalpha1 mediates the normal differentiation-promoting effect of TH on oligodendrocyte precursor cells (OPCs): unlike wild-type OPCs, postnatal TRalpha1-/- OPCs fail to stop dividing and differentiate in response to TH in culture. We also show that overexpression of TRalpha1 accelerates oligodendrocyte differentiation in culture, suggesting that the level of TRalpha1 expression is normally limiting for TH-dependent OPC differentiation. Finally, we provide evidence that the inhibitory isoforms of TRalpha are unlikely to play a part in the timing of OPC differentiation.

MeSH Terms
Animals Cell Differentiation/physiology Immunohistochemistry Mice Mice, Inbred BALB C Oligodendroglia/cytology,metabolism Optic Nerve/embryology,metabolism Protein Isoforms/metabolism Rats Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction Thyroid Hormone Receptors alpha/physiology
Chemicals
Protein Isoforms Thyroid Hormone Receptors alpha
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Billon Nathalie
MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK. n.billon@ucl.ac.uk
Jolicoeur Christine
Tokumoto Yasuhito
Vennström Björn
Raff Martin
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/cdf662
Email
n.billon@ucl.ac.uk
Published
2002-12-02
Pages
6452-60
Language
English
Region
England
NLM ID
8208664
PMCID
PMC136965
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/cdf662 PMC Full Text View journal details
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