Our lab studies the coordination of the cell division cycle and development. The coordination of cellular division, growth and differentiation are crucial to the proper development and functioning of multicellular organisms. 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. This process is called endoreplication or endoreduplication. Endoreplication occurs in many cell types important for agriculture or human health: platelet-producing megakaryocytes and placental trophoblast cells in mammals, and cereal endosperm and cotton fibers in plants. Endoreplication in nitrogen-fixing root nodules of legumes is essential for symbiotic nitrogen fixation, and recent work indicates that endoreplication stabilizes the commitment to differentiated cell fate.
We use the unicellular leaf hairs (trichomes) of Arabidopsis thaliana as a model for studying endoreplication, the cell cycle and cell differentiation. The switch from a mitotic cell cycle to an endoreplication cell cycle requires suppression of mitotic cyclin-dependent kinase activity. We have discovered a new family of plant-specific cyclin-dependent kinase inhibitors, the SIAMESE-RELATED (SMR) family. The defining member of this family, SIAMESE (SIM), is required for suppression of mitosis and initiation of endoreplication cycles during trichome development. SIM works in concert with the Anaphase-Promoting Complex/Cyclosome (APC/C) to establish endoreplication cycles. Our lab is investigating the mechanisms by which SIM and the APC/C initiate endoreplication cycles using genetic, biochemical and cell biological approaches.
All plant genomes encode multiple SMRs, and there is good evidence that this protein family plays diverse roles in regulating the cell cycle during plant development. Thus, our work is likely to give insight into mechanisms of plant growth with important implications for agriculture—for example, as noted above, symbiotic nitrogen fixation in legumes requires endoreplicated plant cells. In addition, initiation of endoreplication requires suppression of the G2/M transition in the mitotic cycle. This transition is poorly understood in all organisms, including animals. Thus insights gained into regulation of the plant G2/M transition may give insights into regulation of the animal cell cycle, and may even lead to information related to diseases of the cell cycle, such as cancer.
Kumar, N., Larkin, J.C. 2017. “Why Do Plants Need So Many Cyclin-Dependent Kinase Inhibitors?” Plant Signaling and Behavior, http://dx.doi.org/10.1080/15592324.2017.1282021
Larkin, J.C., Dassanayake, M. 2017. “Making Plants Break a Sweat: the Structure, Function, and Evolution of Plant Salt Glands.” Frontiers in Plant Biology, In Press.
Hamdoun, S., Zhang, C., Gill, M., Kumar, N., Churchman, M., Larkin, J.C., Kwon, A., Lu, H. 2016. “Differential Roles of Two Homologous Cyclin-Dependent Kinase Inhibitor Genes in Regulating Cell Cycle and Innate Immunity in Arabidopsis.” Plant Physiol., doi: http:/ / dx. doi. org/ 10. 1104/ pp. 15. 01466.
Kumar, N., Harashima, H, Kalve, S., Bramsiepe, J., Wang, K., Sizani, B.L., Bertrand, L.L., Johnson, M.C., Faulk, C., Dale, R. Simmons, L.A., Churchman, M.L., Sugimoto, K. Kato, N., Dassanayake, M., Beemster, G., Schnittger, A., Larkin, J.C. 2015. “Functional Conservation in the SIAMESE-RELATED Family of Cyclin-Dependent Kinase Inhibitors in Land Plants.” Plant Cell doi: 10.1105/tpc.15.00489
Yi, D., Kami, C.L.A., Cools, T., Vanderauwera, S., Takahashi, N., Okusuima, Y., Eekhout, T., Yoshiyama, K.O., Larkin, J.C., Van den Daele, H., Britt, A., Umeda, M. and De Veylder, L. 2014. “The Arabidopsis thaliana SIAMESE-RELATED cyclin-dependent kinase inhibitors SMR5 and SMR7 control the DNA damage checkpoint in response to reactive oxygen species.” Plant Cell doi:10.1105/tpc.113.118943
Kasili R., Huang, C., Walker J.D., Simmons L.A., Zhou, J., Faulk, C., Hülskamp M., and Larkin, J.C. 2011. “BRANCHLESS TRICHOMES Links Cell Shape and Cell Cycle Control in Arabidopsis Trichomes.” Development 138:2379-2388.
Bramsiepe J., Wester, K., Weinl, C, Roodbarkelari, F., Kasili, R., Larkin J.C., Hülskamp, M., and Schnittger, A. 2010. “Endoreplication controls cell fate maintenance.” PLoS Genetics 6: e1000996.
Kasili R., Walker J.D., Simmons L.A., Zhou J., De Veylder L., and Larkin, J.C. 2010 “SIAMESE cooperates with a CDH1-like protein to establish endoreplication.” Genetics 185: 257–268.
Churchman M.L., Brown M.L., Kato N., Kirik V., Hulskamp M., Inze D., De Veylder L., Walker J.D., Zheng Z., Oppenheimer D.G., Gwin T., Churchman J., and Larkin J. C. 2006. “SIAMESE, a Plant-Specific Cell Cycle Regulator, Controls Endoreplication Onset in Arabidopsis thaliana.” Plant Cell 18: 3145-3157.
Larkin, J.C., Brown, M., and Schiefelbein, J. 2003. “How do cells know what they want to be when they grow up? Lessons from epidermal patterning in plants.” Annu. Rev. Plant Biology 54: 403-430.