Roles for p53 and p73 during oligodendrocyte development
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Roles for p53 and p73 during oligodendrocyte development 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 PDGE 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.
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differentiation; oligodendrocyte; p53; p63; p73; rat Rat optic-nerve; glial progenitor-cell; thyroid-hormone; precursor cells; transcription factors; receptor superfamily; spontaneous tumors; gene-expression; growth-factor; in-vitro
DEVELOPMENT, 2004, 131 (6), pp. 1211 - 1220