Lynn Cooley PhD

C. N. H. Long Professor of Genetics and Professor of Cell Biology and of Molecular, Cellular, and Developmental Biology; Director, Combined Program in the Biological & Biomedical Sciences

Research Interests

Molecular Genetics of Drosophila Oogenesis; Actin Cytoskeleton Regulation; Drosophila; Oogenesis; Ring Canal; Ovarian Muscle Function

Research Summary

We are interested in the cellular mechanisms that underlie polarity and cell growth during development. Our research is focused on understanding how maternal components are made and delivered to oocytes during Drosophila oogenesis. Using mutants with incomplete oocyte growth, we have discovered key roles for the actin cytoskeleton. For example, the ring canals connecting growing oocytes with their nurse cells are stabilized by a special population of bundled actin filaments.

The dramatic growth of ring canals during oogenesis requires both actin polymerization and depolymerization, making ring canals a valuable model for in vivo actin dynamics. The polarized movement of maternal mRNA and protein through ring canals from nurse cells to the oocyte is highly regulated. We identified proteins specifically targeted to the oocyte by GFP protein trapping; we are determining the mechanism of targeting using both live imaging and molecular dissection of the proteins to identify localization signals.

Extensive Research Description

Gametes are the ultimate stem cells with the capacity to produce entire new organisms. We study cellular mechanisms of gamete development using Drosophila as a model system. We are focused on the development of female germline cells, from their early differentiation into oocytes or nurse cells, through the control of oocyte growth during oogenesis. In addition, we study the role of ovarian muscles in the progression of developing egg chambers through the ovary.

Early germline development in animals, including flies, relies on a non-canonical form of mitosis. Daughters of germline stem cells undergo a tightly controlled number of mitotic cell divisions with incomplete cytokinesis so that bridges of cytoplasm remain to connect clusters of sister cells. These residual connections are transformed into stable intercellular junctions called ring canals, which are needed for oocyte growth.

In females, this transformation involves recruiting a highly dynamic actin cytoskeleton and many associated actin-binding proteins. Using a variety of genetic and molecular approaches, we have identified many ring canal proteins, and we are actively working toward characterizing their functions. We are also studying the role of ring canals in the polarized transport of maternal mRNAs, proteins and organelles from nurse cells and to the oocyte.

While ring canals are ubiquitous in germline cells, their presence and function in somatic cells are largely unexplored. In order to understand how these fascinating structures contribute to the biology of non-germline cells, we are characterizing somatic ring canals in epithelial cells of the Drosophila ovary and imaginal discs using cell biology and genetics.

Recently we discovered a novel muscle type in the Drosophila ovary that contains striated sarcomeres, but only a single nucleus. This indicates the muscles did not form by typical myoblast fusion. Importantly, the presence of one nucleus means we can use powerful genetic clonal analysis to analyze the effects of mutations affecting muscle proteins, including those associated with human musclular dystrophy. In addition, we can study proliferation of these muscles in adults and the pool of progenitor stem cells that supply new muscle cells in adults.

Selected Publications