Regulation of the Cell Cycle During Development and the Checkpoint Response


The goal of our research is to elucidate the regulatory pathways that control eukaryotic cell proliferation, particularly in relation to embryogenesis and development. Eukaryotic cells, from yeast to human, divide by following a series of events known as the cell cycle. In turn, advancement through the cell cycle is driven by a family of cyclin dependent kinases (Cdks). Strict regulation of the Cdks ensures that cell proliferation takes place only in the proper temporal order and only under the proper conditions. For example, the cell cycle of a normal cell will stop or slow its progression in response to specific developmental signals or perceived damage to cellular components. When this regulation fails, developmental abnormalities and disease states such as cancer can arise. In our research, we use the model system Xenopus (African clawed frog) to study these problems. Xenopus offers the advantage of combining both biochemical and developmental approaches. For example, the cell cycle can be reconstituted with Xenopus egg extracts, thus providing a powerful assay for studying the action of recombinant or purified cell cycle regulators. In addition, Xenopus embryos are easily obtained and cultured, and their size and external development makes them ideal for microinjection and micromanipulation. Finally, due to the highly conserved nature of the cell cycle regulatory apparatus, it is possible to use complementation of more genetically tractable organisms (fission and budding yeast) to study the action of Xenopus proteins. Thus, our laboratory utilizes a multifaceted experimental approach to elucidate how various Cdk regulatory mechanisms control cell cycle progression.