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Analysis of Cell Cycle Position in Mammalian Cells
Published on: January 21, 2012
Transforming growth factor beta 1 promotes cell cycle exit through the cyclin-dependent kinase inhibitor p21 in the
Julie A Siegenthaler1, Michael W Miller
1Department of Neuroscience and Physiology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA.
Abstract:
During cortical neurogenesis, cell proliferation and cell cycle exit are carefully regulated to ensure that the appropriate numbers of cells are produced. The antiproliferative agent transforming growth factor beta1 (TGFbeta1) and its receptors are endogenously expressed in proliferative zones of the developing cerebral cortex, thus implicating the growth factor in cell cycle regulation. The present study tested the hypothesis that TGFbeta1 promotes cell cycle exit in the cortical ventricular zone (VZ) through modulation of cell cycle protein expression, in particular cyclin D1 and the cyclin-dependent kinase inhibitors p27 and p21. Although it did not affect the length of the cell cycle, TGFbeta1 decreased the fraction of VZ-cycling cells by 21% and increased the number of VZ cells exiting the cell cycle a commensurate 24%. TGFbeta1 selectively increased the expression of p21 in the VZ. In addition, high p21 expression levels were observed in VZ cells as they exited the cell cycle, and TGFbeta1 increased the number p21-positive cells exiting the cell cycle. Collectively, these data show the following: (1) TGFbeta1 promotes cell cycle exit, (2) p21 upregulation is correlated with cell cycle exit, and (3) TGFbeta1-induced cell cycle exit is mediated by p21.
Insights
Transforming growth factor beta1 (TGFbeta1) promotes cell cycle exit during brain development. This process is linked to increased expression of the p21 protein in neural progenitor cells.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Cortical neurogenesis requires precise regulation of cell proliferation and cell cycle exit.
- Transforming growth factor beta1 (TGFbeta1) is present in developing cerebral cortex regions and is implicated in cell cycle control.
Purpose of the Study:
- To investigate if TGFbeta1 promotes cell cycle exit in the cortical ventricular zone (VZ).
- To determine if TGFbeta1 modulates cell cycle proteins, specifically cyclin D1, p27, and p21.
Main Methods:
- Treatment of cortical VZ cells with TGFbeta1.
- Analysis of cell cycle length, fraction of cycling cells, and cell cycle exit.
- Assessment of cell cycle protein expression (cyclin D1, p27, p21) via quantitative analysis.
Main Results:
- TGFbeta1 treatment reduced the fraction of VZ-cycling cells by 21% and increased cell cycle exit by 24%.
- TGFbeta1 selectively upregulated p21 expression in the VZ.
- High p21 expression correlated with VZ cells exiting the cell cycle, and TGFbeta1 increased the number of p21-positive cells exiting the cell cycle.
Conclusions:
- TGFbeta1 actively promotes cell cycle exit during cortical development.
- Upregulation of p21 is a key event associated with TGFbeta1-induced cell cycle exit.
- The mechanism of TGFbeta1-induced cell cycle exit involves the p21 protein.
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