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Medical Research Council Developmental Neurobiology Programme, Medical Research Council Laboratory for Molecular Cell
Biology, and the Biology Department, University College London, London WC1E 6BT, United Kingdom
We have used clonal analysis and time-lapse
video recording to study the proliferative behavior of
purified oligodendrocyte precursor cells isolated from
the perinatal rat optic nerve growing in serum-free cultures. First, we show that the cell cycle time of precursor cells decreases with increasing concentrations of PDGF, the main mitogen for these cells, suggesting that
PDGF levels may regulate the cell cycle time during development. Second, we show that precursor cells isolated from embryonic day 18 (E18) nerves differ from
precursor cells isolated from postnatal day 7 (P7) or
P14 nerves in a number of ways: they have a simpler morphology, and they divide faster and longer before
they stop dividing and differentiate into postmitotic oligodendrocytes. Third, we show that purified E18 precursor cells proliferating in culture progressively
change their properties to resemble postnatal cells, suggesting that progressive maturation is an intrinsic property of the precursors. Finally, we show that precursor
cells, especially mature ones, sometimes divide unequally, such that one daughter cell is larger than the
other; in each of these cases the larger daughter cell divides well before the smaller one, suggesting that the
precursor cells, just like single-celled eucaryotes, have
to reach a threshold size before they can divide. These
and other findings raise the possibility that such stochastic unequal divisions, rather than the stochastic
events occurring in G1 proposed by "transition probability" models, may explain the random variability of
cell cycle times seen within clonal cell lines in culture.
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