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First published online 11 February 2004
doi: 10.1242/dev.01035

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: dev.01035v1 131/6/1211    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Billon, N. Articles by Raff, M. Search for Related Content PubMed PubMed Citation Articles by Billon, N. Articles by Raff, M. Social Bookmarking                         What's this?

Roles for p53 and p73 during oligodendrocyte development

Nathalie Billon^1,4,, Alessandro Terrinoni², Christine Jolicoeur^1,*, Afshan McCarthy³, William D. Richardson⁴, Gerry Melino^2,5 and Martin Raff¹

¹ MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, London WC1E 6BT, UK
² Biochemistry Laboratory, IDI-IRCCS, c/o Tor Vergata University, Via Montpellier, 1, 00133 Roma, Italy
³ Breakthrough Breast Cancer Centre, London Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
⁴ Wolfson Institute for Biomedical Research, University College London, London WC1E 6BT, UK
⁵ MRC Toxicology Unit, Hodgkin Building, Leicester University, Lancaster Road, Leicester LE1 9HN, UK

Author for correspondence (e-mail: billon{at}unice.fr)

Accepted 10 December 2003

Oligodendrocytes make myelin in the vertebrate central nervous system (CNS). They develop from oligodendrocyte precursor cells (OPCs), most of which divide a limited number of times before they stop and differentiate. OPCs can be purified from the developing rat optic nerve and stimulated to proliferate in serum-free culture by PDGF. They can be induced to differentiate in vitro by either thyroid hormone (TH) or PDGF withdrawal. It was shown previously that a dominant-negative form of p53 could inhibit OPC differentiation induced by TH but not by PDGF withdrawal, suggesting that the p53 family of proteins might play a part in TH-induced differentiation. As the dominant-negative p53 used inhibited all three known p53 family members - p53, p63 and p73 - it was uncertain which family members are important for this process. Here, we provide evidence that both p53 and p73, but not p63, are involved in TH-induced OPC differentiation and that p73 also plays a crucial part in PDGF-withdrawal-induced differentiation. This is the first evidence for a role of p73 in the differentiation of a normal mammalian cell.

Key words: Differentiation, Oligodendrocyte, p53, p63, p73, Rat

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