Margaret de Cuevas

Assistant Professor

The goal of my research is to understand how gametes develop in animals.  In many animal species, including insects, frogs, mice and humans, gametes are formed by a similar developmental pathway.  After migrating to the site of the developing gonad, each germ cell embarks on a special program of cell division to form a cyst.  Germline cysts are clusters of cells that are formed by rounds of mitosis with incomplete cytokinesis; thus, the cells in the cyst remain connected to one another by intercellular bridges.  Following cyst formation, the cells enter meiosis, disconnect from one another, and finish developing into mature eggs or sperm.  Because the process of cyst formation is highly conserved in evolution, it is likely that cysts play an important role in gamete development.

My lab uses the Drosophila ovary as a model system for understanding the cellular and molecular mechanisms controlling cyst formation.  We focus in particular on the fusome, an unusual cytoplasmic organelle found in developing cysts in Drosophila and other insects, which is composed of a network of endoplasmic reticulum-like tubules, cytoskeletal proteins, and cell cycle regulatory proteins.  Genetic studies have shown that the fusome plays an essential role in cyst formation and oocyte development; flies with mutations that disrupt the fusome make aberrant cysts and fail to produce viable eggs.  We are using a variety of approaches - including cell biology, molecular genetics, and biochemistry - to investigate the structure and function of the fusome.  Current areas of research include: 1) investigating fusome and cytoskeletal dynamics in living ovaries using timelapse confocal microscopy; 2) developing methods for biochemical purification of fusomes; and 3) using genetic screens to identify genes required for fusome and cyst development.  We are also taking advantage of the recently completed Drosophila genome sequence to identify candidate genes of interest.  Through these experiments, we hope to gain insight into the regulation of germ cell division and differentiation in Drosophila as well as in other organisms, including humans.

Research articles:

N.C. Grieder, M. de Cuevas and A.C. Spradling.  2000.  The fusome organizes the microtubule network during oocyte differentiation in Drosophila.  Development 127: 4253-4264.

M.A. Lilly, M. de Cuevas and A.C. Spradling.  2000.  Cyclin A associates with the fusome during germline cyst formation in the Drosophila ovary.  Dev. Biol.218: 53-63.

M. de Cuevas and A.C. Spradling.  1998.  Morphogenesis of the Drosophila fusome and its implications for oocyte specification.  Development 125: 2781-2789.

M. de Cuevas, J.K. Lee and A.C. Spradling.  1996.  a-spectrin is required for germline cell division and differentiation in the Drosophila ovary.  Development 122: 3959-3968.

Review articles:

M.E. Pepling, M. de Cuevas and A.C. Spradling.  1999.  Germline cysts: a conserved phase of germ cell development?  Trends Cell Biol. 9: 257-262.

M. de Cuevas, M.A. Lilly and A.C. Spradling.  1997.  Germline cyst formation in Drosophila. Ann. Rev. Genet. 31: 405-428.

People currently in the lab:

Veronica Linares (undergraduate)
Rachel Fasnacht (faculty research assistant)

Go to Dr. de Cuevas Lab web site (under development)