Nuclear Division in Drosophila

One of the most fascinating questions in cell biology today is how the cell coordinates the many events regulating nuclear division. Intensive research has been directed toward identifying molecules participating in this process in many different organisms, especially because an extraordinary degree of structural and functional conservation across evolution of the signaling molecules is involved. This is most dramatically demonstrated by the finding that molecules found in humans can perform the same functions in yeast! Thus, the study of mitosis and cell division in various species promises to help elucidate general principles governing cell division that apply to humans as well.

We are using the fruit fly, Drosophila melanogaster, to investigate molecules involved in regulating nuclear division. We have identified a protein (2A) that shows a dynamic cell cycle-specific distribution pattern. The 2A protein localizes with the microtubule spindle fibers at metaphase and to the chromatin and/or nuclear matrix at interphase. Consequently, Cherice Conley, John Fillman, Pallavi Kumar, Andrea Silvers, and I have been working to determine the full-length sequence of this new protein and to ascertain its function in the cell cycle. Ultimately we want to understand the role this protein plays in nuclear division. David Robinson has been working on establishing embryo microinjection techniques in the laboratory, and Phil Irwin will be injecting antibody into embryos to determine whether he can block protein function, and if so, what effect this has on nuclear division. In addition, we will be generating mutations in this and other genes, and analyzing the resulting phenotypes. Working toward this goal, Ife Fadeyi has been immunostaining a previously described mutant that undergoes subsequent rounds of DNA synthesis without intervening chromosomal divisions, resulting in one or two "giant" nuclei.

Visualizing the 2A protein pattern in such embryos may clarify the protein's function. One of the powerful advantages to the Drosophila model system is that, once we have obtained a mutation in our gene, we can use genetic screens to identify other components in the pathway that may also be involved in controlling nuclear division. This promises to enhance our basic understanding about how growth control and cell division are regulated, which ultimately may prove helpful in understanding and treating human cancers.