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

Development 131, 1211-1220 (2004)
Published by The Company of Biologists 2004
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Roles for p53 and p73 during oligodendrocyte development

Nathalie Billon1,4,{dagger}, Alessandro Terrinoni2, Christine Jolicoeur1,*, Afshan McCarthy3, William D. Richardson4, Gerry Melino2,5 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

{dagger} 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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