Firstly I examined pRb, which is a key negative regulator of cell proliferation. It prevents cells from progressing into S phase by inactivating transcription transcription factors essential for DNA synthesis until it is appropriate for the cell to divide. In addition to implementing cell cycle arrest during differentiation, and independently of this function, pRb is required during myogenesis to promote the full transcriptional activity of the muscle differentiation factor MEF2. However, I have shown by overexpression and depletion studies that it is not required for neural differentiation during early <i>Xenopus</i> embryogenesis. Subsequently I have investigated the roles of cyclins, CDKs and CDK1s in regulating differentiation. I have demonstrated by overexpression studies that cyclin A/CDK2 regulates both cell cycle progression and differentiation in a tissue-specific manner. In contrast, overexpression of another G1 cyclin, cyclin E, with CDK2 causes loss of nuclear DNA and apoptosis. The <i>Xenopus</i> CDKI p27<sup>Xic1</sup> regulates the activity of CDK2 and has been shown to play two distinct roles in regulating the cell cycle and in promoting muscle and neural differentiation. In contrast to cyclin A/CDK2, I have demonstrated by overexpression and depletion studies that, while p27<sup>Xic1<i> </i></sup>regulates proliferation in the epidermis, its effect on epidermal differentiation is minimal. Finally, I studied further potential regulators of the cell cycle in the ectoderm. I have shown that both p63, a p53 family member, and members of the myc family inhibit proliferation in the epidermis. Moreover, I have shown that c-myc and N-myc regulate the size of the neural plate. In conclusion, I demonstrate that differentiation cell cycle molecules have the potential to regulate both cell cycle progression and differentiation, but that each achieves this in a distinct manner.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:598009 |
| Date | January 2004 |
| Creators | Cosgrove, R. A. |
| Publisher | University of Cambridge |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
Page generated in 0.0024 seconds