Editors' ChoiceDevelopment

Taking the Time to Determine Cell Fate

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Science's STKE  25 Nov 2003:
Vol. 2003, Issue 210, pp. tw455-TW455
DOI: 10.1126/stke.2102003TW455

Calegari and Huttner exposed mouse embryos to an inhibitor of cyclin-dependent kinases (CDKs) to investigate the hypothesis that an increase in the length of the cell cycle might be a cause (rather than a consequence) of neuronal differentiation. During the development of multicellular organisms, cell division can yield daughter cells with different fates. This is associated with unequal distribution of cell fate determinants to daughter cells; however, such an unequal distribution does not always lead to distinct cell fates. Neuroepithelial (NE) cells, which give rise to all of the neurons in the mammalian central nervous system, switch from a proliferative to a neuron-generating mode in a distinct spatiotemporal pattern, a switch associated with an increase in the G1 phase of the cell cycle. Calegari and Huttner grew whole mouse embryos in vitro in the presence of the CDK inhibitor olomoucine or an inactive isomer. Moderate concentrations of olomoucine slowed NE cell cycle length, assessed by cumulative labeling with bromodeoxyuridine, without increasing apoptosis, affecting cell size, or blocking the cell cycle. This was associated with a premature switch of NE cells from proliferative to neuron-generating mode and with the premature appearance of neurons, both assessed by immunofluorescence analysis of specific markers (TIS21 and MAP2, respectively). The authors proposed a model in which the interaction between the amount of particular cell fate determinants and the length of time over which such determinants act during the cell cycle determines cell fate and suggested that TIS21, which appears in neuron-generating cells and prolongs G1, itself promotes neurogenesis.

F. Calegari, W. B. Huttner, An inhibition of cyclin-dependent kinases that lengthens, but does not arrest, neuroepithelial cell cycle induces premature neurogenesis. J. Cell Sci. 116, 4947-4955 (2003). [Abstract] [Full Text]

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