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The Journal of Neuroscience, November 10, 2004, 24(45):10201-10210; doi:10.1523/JNEUROSCI.3246-04.2004
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Development/Plasticity/Repair
Insulin-Like Growth Factor-I Accelerates the Cell Cycle by Decreasing G1 Phase Length and Increases Cell Cycle Reentry in the Embryonic Cerebral Cortex
Rebecca D. Hodge,1 A. Joseph D'Ercole,2 andJohn R. O'Kusky1 1Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada, V5Z 4H4, and 2Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7220
Neurogenesis in the developing cerebral cortex of mice occurs in the dorsal telencephalon between embryonic day 11 (E11) and E17, during which time the majority of cortical projection neurons and some glia are produced from proliferating neuroepithelial cells in the ventricular zone. The number of cells produced by this process is governed by several factors, including cell cycle kinetics and the proportion of daughter cells exiting the cell cycle after a given round of cell division. The in vivo effects of IGF-I on cell cycle kinetics were investigated in nestin/IGF-I transgenic (Tg) embryos, in which IGF-I is overexpressed in the cerebral cortex and dorsal telencephalon. These Tg mice have been shown to exhibit increased cell number in the cortical plate by E16 and increased numbers of neurons and glia in the cerebral cortex during postnatal development. Cumulative S phase labeling with 5-bromo-2'-deoxyuridine revealed a decrease in total cell cycle length (TC) in Tg embryos on E14. This decrease in TC was found to result entirely from a reduction in the length of the G1 phase of the cell cycle from 10.66 to 8.81 hr, with no significant changes in the lengths of the S, G2, and M phases. Additionally, the proportion of daughter cells reentering the cell cycle was significantly increased by 15% in Tg embryos on E14-E15 compared with littermate controls. These data demonstrate that IGF-I regulates progenitor cell division in the ventricular zone by reducing G1 phase length and decreasing TC but increases cell cycle reentry.
Key words: insulin-like growth factor-I; IGF-I; mitosis; neurogenesis; transgenic mice; ventricular zone
Received Aug 7, 2004; revised September 24, 2004; accepted October 1, 2004.
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