R. Mako Saito
Assistant Professor of Genetics
Research Areas: Developmental Biology, Genetics
Developmental Control of Cell Cycle in C. elegans
The ability of an organism to control the proliferation of its cells is crucial for correct development. Organogenesis commonly requires that the timing of proliferation and differentiation be coordinated between cells derived from several independent origins. Thus, cells must be able to efficiently communicate with their neighbors. Defects in a cell's ability to receive or respond to these extracellular signals can result in developmental defects and cancer. Therefore, to understand the general mechanisms cells use to regulate their cell-cycle machinery in response to environmental signals we use genetic studies to dissect the developmental regulation of cell-cycle regulation in C. elegans.
Our lab studies several aspects of cell-cycle regulation using C. elegans as a model. Using the invariant wild type cell lineage as a reference, we can identify mutants that are defective in the arrest or entry of specific cell divisions. Studies of the vulval precursor cells or VPCs have identified roles for the highly conserved p27kip and pRb genes in developmentally regulated cell-cycle arrest. Interestingly, a previously unrecognized function of the Cdc14 phosphatase in the control of cell-cycle entry was revealed in our studies. Future studies aim to further uncover the mechanisms used to control cell divisions during development.
Visit the Saito Lab website.
Publications
Clayton, J.E., van den Heuvel, S.J. and Saito, R.M. Transcriptional control of cell-cycle quiescence during C. elegans development. Dev Biol 313:603-613 (2008). PMID: 18082681
Saito, R.M., A. Perreault, B. Peach, J.S. Satterlee and S. van den Heuvel. 2004. The cdc-14 phosphatase controls developmental cell-cycle arrest in C. elegans. Nature Cell Biology. 6: 777-83.
Miley, G.R.K., D. Fantz, D. Glossip, X. Lu, R.M. Saito, T. Inoue, R. Palmer, S. van den Heuvel, P. Sternberg and K. Kornfeld. 2004. Identification of residues of the Caenorhabditis elegans LIN-1 ETS domain that are necessary for DNA binding and regulation of vulval fates. Genetics. 167.
Yajnik, V., C. Paulding, R. Sordella, A.I. McClatchey, R.M. Saito, D.C.R. Wahrer, P. Reynolds, D.W. Bell, R. Lake, S. van den Heuvel, J. Settleman, and D.A. Haber . 2003. DOCK4, a GTPase Activator, Is Disrupted during Tumorigenesis. Cell. 112:673-684.
Saito, R.M. and S. van den Heuvel. 2002. Malignant worms: what cancer research can learn from C. elegans. Cancer Investigation. 20:264-275.