During the development of multicellular organisms, cell differentiation must be tightly coordinated with cell division. In animals, loss of control of cell division leads to cancer. In some cell types, a modified cell cycle occurs during differentiation in which the DNA is replicated without concomitant cell division, resulting in an increase in nuclear DNA content. The role of this process, termed endoreplication, is poorly understood. In previous work using Arabidopsis leaf hairs (trichomes) as a model for cell differentiation, the SIAMESE (SIM) gene was shown to be required to repress mitosis and establish endoreplication. The SIM gene has now been isolated by the PI's group, and the predicted gene product is a good candidate for a direct regulator of cyclin-dependant kinase activity, which plays a key regulatory role in the cell cycle. Arabidopsis has a small gene family of about four SIM-related proteins, and homologs exist in other plant species. The overall goals of this proposal are to determine the function of SIM in the regulation of endocycling during trichome development, and to test the hypothesis that members of the SIM gene family may play a role in integrating the cell cycle with developmental signals in other aspects of plant growth, such as flower, root, and vascular development. It is expected that this work will lead to a better understanding of the mechanisms coordinating the cell cycle with plant development. Additionally, the proposed work will play a role in the education of graduate students, undergraduates, and high school students from a wide diversity of backgrounds.