Research Projects

Company of Biologists Ltd. 2000Above: syncytial cyst of elongating spermatids stained for DNA (blue), F-actin (red) and anillin (green)

Drosophila spermatids develop as cysts of interconnected cells. During differentiation, these bundles of spermatids elongate, condense their DNA, form acrosomes and then undergo a process of individualization into mature sperm.

We are studying several aspects of the membrane and cytoskeletal remodeling that underlie these morphogenetic processes. For example, plasma membrane surface area increases during both cytokinesis and spermatid bundle elongation. Some mutants, such as fwd, affect only cytokinesis, whereas others affect both processes. These latter mutations affect known secretory proteins including Drosophila syntaxin-5 are also defective in spermatid bundle elongation.

We are currently testing the hypothesis that these mutants have a more global defect in secretion than does fwd.

The formation of stable germ line intercellular bridges illustrates that the resolution of cytokinesis is under developmental control.

Drosophila male germ line ring canals contain at least three families of proteins that are also found in germ line cleavage furrows: anillin, the septins and one or more tyrosine kinases (Hime, Brill and Fuller, J. Cell Sci.1996).

To learn more about the developmental control of cytokinesis, we plan to use a combination of biochemical purification techniques, proteomics and genomics to identify other proteins required for intercellular bridge formation.

From our experiments on fwd, we know that PI(4)P synthesis is crucial for male germ cell cytokinesis (Brill, Hime, Scharer-Schuksz, Fuller, Development 2000). Surprisingly, however, fwd is not an essential gene. As PI lipids are widely believed to be fundamental to the control of cell proliferation, we hypothesize that another PI4K must carry out any essential roles in PI lipid biosynthesis. Flies contain two additional predicted PI4Ks.

We are carrying out genetic screens to identify mutations in these genes so we can learn how these lipid kinases affect cell division during Drosophila development.

Recent Publications

Wei, H.-C., Rollins, J., Fabian, L., Hayes, M., Polevoy, G., Bazinet, C. and Brill, J. A. (2008) Depletion of plasma membrane PtdIns (4,5) P2 reveals essential roles for phosphoinositides in flagellar biogenesis. J Cell Science, 121: 1076-84.**Cover article.

Wong, R., Fabian, L., Forer, A. and Brill, J. A. (2007) Phospholipase C and myosin light chain kinase inhibition define a common step in actin regulation during cytokinesis. BMC Cell Biology 8: 15.

Parsons, A. B., Lopez, A., Givoni, I. E., Williams, D. E., Gray, C., Porter, J., Chua, G., Sopko, R., Brost, R. L., Ho, C.-H., Wang, J., Ketela, T., Brenner, C., Brill, J. A., Fernandez, G. E., Lorenz, T. C., Payne, G. S., Ishihara, S., Ohya, Y., Andrews, B., Hughes, T. R., Frey, B. J., Graham, T. R , Andersen, R. J. and Boone, C. (2006) Exploring the mode-of-action of bioactive compounds by chemical-genetic profiling in yeast. Cell 126: 611-25.

Jin, Z., Homola, E.M., Goldbach, P., Choi, Y.H., Brill, J. A. and Campbell, S.D. (2005) Drosophila Myt1 is a Cdk1 inhibitory kinase that regulates multiple aspects of cell cycle behavior during gametogenesis. Development 132: 4075-85.

Wong, R., Hadjiyanni, I., Wei, H.-C., Polevoy, G., McBride, R., Sem, K.-P. and Brill, J.A. (2005) PIP2 hydrolysis and calcium release are required for cytokinesis in Drosophila spermatocytes. Current Biology 15: 1401-06. **Featured in Nature, “Research Highlights,” Aug. 18, 2005, Janetopoulos & Devreotes, J Cell Biol (2006) 174:485-90, and Logan & Mandato, Biol Cell (2006) 98: 377-88.

Saul, D., Fabian, L., Forer, A. and Brill, J. A. (2004) Continuous phosphatidylinositol metabolism is required for cleavage of crane-fly spermatocytes. J Cell Sci117: 3887-96. **Cover article. Featured in Riggs et al., Trends in Cell Biology (2005) 15:92-101. Cover illustration published in textbook, Cell and Molecular Biology, 5th edition, by G. Karp.

Wei, H.-C., Sanny, J., Shu, H., Baillie, D. L., Brill, J. A., Price, J. V. and Harden, N. (2003) The Sac1 lipid phosphatase regulates cell shape change and the JNK cascade during dorsal closure in Drosophila. Current Biology13: 1882-87.

Xu, H., Brill, J.A., Hsien, J., McBride, R., Boulianne, G.L., Trimble, W.S. (2002) Syntaxin 5 is required for cytokinesis and spermatid differentiation in Drosophila. Developmental Biology 251: 294-306. View online abstract

Brill, J.A., Hime, G.R., Scharer-Schukz, M., Wolf, N. and Fuller, M.T. (2000) A phospholipid kinase regulates actin organization and intercellular bridge formation during germline cytokinesis. Development 127: 3855-3864. Download PDF 422 KB

Molina, I., Baars, S., Brill, J.A., Hales, K.G., Fuller, M.T. and Ripoll, P. (1997) A chromatin-associated kinesin-related protein required for normal mitotic chromosome segregation in Drosophila. J. Cell Biol. 139: 1361-1371. View online article

Journal of Cell Science cover - Dec. 1996

Hime, G.R.,* Brill, J.A.,* and Fuller, M.T. (1996) Assembly of ring canals in the male germline from structural components of the contractile ring. J. Cell Sci. 109: 2779-2788. Download PDF 545 KB

*Co-first authors who contributed equally to the work.

A detailed list of Dr. Brill's publications is available on Pub Med.