Lynn Cooley

Professor of Genetics and Cell Biology; Director, Combined Programs in Biological and Biomedical Sciences

B.A. Connecticut College, 1976
Ph.D. University of Texas, 1984

Research Interests:

Molecular Genetics of Drosophila Oogenesis
Actin Cytoskeleton Regulation

Honors:

Pew Scholar Award

Changes in cell shape and motility that occur throughout the development of an organism require dynamic alterations of the cytoskeleton in response tosignaling pathways. We are studying cytoskeletal reorganization during Drosophila egg chamber development, and the regulatory pathways that control cytoskeletal rearrangement.

Current Research

Each Drosophila oocyte develops within an egg chamber that consists of one oocyte and fifteen nurse cells surrounded by a layer of epithelial follicle cells. The oocyte and nurse cells are connected by large cytoplasmic bridges called ring canals. Ring canals also exist between developing oogonia and spermatocytes in a wide variety of species, including humans. In Drosophila, the oocyte is transcriptionally inactive and relies on the nurse cells to transport cytoplasmic components through the ring canals. We have taken a genetic approach to identifying genes required for cytoplasm transport by studying a small set of mutants in which incomplete cytoplasm transport results in the production of severely undersized eggs. Our work on this class of genes has focused our attention on ring canals that provide the pathway for cytoplasm flow and on networks of cytoplasmic actin filaments that form in nurse cells just before final nurse cell contraction.

The hu-li tai shao (hts) and kelch genes are involved with assembly and function of ring canals. At least one protein product of each gene is specifically localized to ring canals (see figure). The hts protein is recruited to new ring canals several hours before the kelch protein, suggesting a pathway for ring canal assembly. The hts protein is required for actin filament assembly at the ring canals since hts mutant ring canals lack actin. One goal of our current research is to determine the function of the hts protein, in part by identifying other proteins to which it binds. The kelch protein stabilizes both actin and hts at the ring canal rim. It contains both dimerization and actin binding domains and thus probably functions as an actin filament crosslinking protein. We are currently investigating the function of a human kelch gene.

Three genes (chickadee, quail and singed) are involved with regulating actin assembly. Each of these genes has female sterile alleles in which nurse cell cytoplasmic actin filaments do not form properly. The consequence is that nurse cell nuclear position is not maintained and the nuclei can block the flow of cytoplasm through ring canals. The product of the chickadee gene, profilin, is probably involved with initial events leading to rapid actin filament polymerization. The quail and singed genes each encode proteins that can bundle actin filaments. The singed gene encodes a protein that is homologous to echinoderm fascin and quail encodes an ovary-specific villin-like protein. Although the functions of fascin and villin are biochemically and genetically distinct, we are have found that over-expression of quail protein can compensate for loss of fascin. We are pursuing molecular genetic analysis of these three actin binding proteins; one goal is to dissect the regulatory pathways controlling their function.

The left panel is a drawing of a Drosophila egg chamber showing the position of the oocyte and the nurse cells. Cytoplasm flows into the oocyte through ring canals connecting the nurse cells to the oocyte. The right panel is an egg chamber stained with an antibody to the ring canal-specific hts protein showing the normal complement of 15 ring canals.

Representative Publications:

Foley, K. and Cooley, L. (1998) Apoptosis in late stage Drosophila nurse cells does not require genes within the H99 deficiency. Development 125:1075-1082.

Sokol, N. and Cooley, L. (1999) Drosophila Filamin encoded by the cheerio locus is a component of ovarian ring canals. Current Biology 9: 1221-1230.

Matova, N., Mahajan-Milkos, S., Mooseker, M. and Cooley, L. (1999) The Drosophila villin-like protein quail bundles actin filaments in apoptotic nurse cells. Development 126: 5645-5657.

Adams, J., Kelso, R. and Cooley, L. (2000) The kelch repeat superfamily of proteins: propellers of cell function. Trends in Cell Biology 10: 17-24.

Matova, N. and Cooley, L. (2001) Comparative aspects of animal oogenesis. Devel. Biol. 231: 291-320.

Hudson, A. and Cooley, L. (2002) A subset of dynamic actin rearrangements in Drosophila requires the Arp2/3 complex. J. Cell Biol. 156: 677-687.

Zallen, J.A., Cohen, Y., Hudson, A., Cooley, L., Wieschaus, E. and Schejter, E. (2002) SCAR is a primary regulator of Arp2/3-dependent morphological events in Drosophila. J. Cell Biol. 156: 689-701.

Kelso, R., Hudson, A. and Cooley, L. (2002) Drosophila Kelch regulates actin organization via Src-dependent tyrosine phosphorylation. J. Cell Biol. 156: 703-713.

<lynn.cooley@yale.edu>

Updated 28 March 2002