Gertrud M. Schüpbach
Faculty AssistantLaisa Eimont
- Ph.D., Biology, University of Zurich, Switzerland
- M.S., Biology, University of Zurich, Switzerland
Research AreaCell Biology, Development & Cancer
Research FocusGenetic and molecular analysis of oogenesis in Drosophila melanogaster
The mature egg of Drosophila melanogaster contains information that determines the major axis of the embryo. This information is built into the egg during oogenesis and functions in the early embryo to create a regionally distinct pattern of zygotic gene expression. The work in the laboratory focuses on understanding the nature and distribution of this maternal information. In particular, we are analyzing how this spatial information is built into the egg during oogenesis.
As a first step in the analysis, we carried out screens for female sterile and maternal-effect mutations. Several classes of mutations that affect the pattern of the egg or the body pattern of the embryo were identified. We have subsequently concentrated on mutations in our collection that affect not only the spatial pattern of the embryo but also the pattern of the egg shell. These genes act early during oogenesis to establish the spatial pattern of the egg chamber as a whole, including both the pattern of the egg shell which is produced by the follicle cells situated on the outside of the egg chamber as well as the spatial distribution, or local activation of the maternal cytoplasmic determinants that specify the pattern of the embryo. Mosaic analysis has shown that some of the genes in this class act in the germline itself, while a second group of genes functions in the follicle cells.
The analysis of these genes has demonstrated that cell-cell interactions between germline and follicle cells take place during oogenesis and are important for the establishment of the normal pattern of egg shell and embryo. One of the genes required for the dorsoventral pattern of egg and embryo (torpedo) is homologous to the vertebrate Epidermal Growth Factor receptor (EFGr). This vertebrate protein is known to function as a transmembrane receptor with tyrosine kinase activity. A detailed genetic analysis of this gene has revealed that this receptor tyrosine kinase is used at several different stages in the Drosophila life cycle and promotes different cell communication processes. During oogenesis it is expressed in the follicle cells, and enables the follicle cells to receive dorsoventral patterning signals from the germline. The genes that act in the germline are involved in the production of this germline signal. In particular we found that the gene gurken encodes a protein that has homology to the vertebrate signaling molecule TGF-alpha. Therefore, gurken encodes a ligand for torpedo/Egfr. Interestingly, during oogenesis, the gurken RNA becomes localized to the future dorsal side of the oocyte. The localized gurken RNA produces a high concentration of Gurken protein on the dorsal side of the egg. Localization of gurken RNA to one side of the oocyte therefore represents a first step in a cascade of events that determines dorsoventral pattern of the egg. We are conducting further experiments to analyze the mechanisms that lead to the asymmetric localization of the gurken RNA.
Once activated, the torpedo receptor tyrosine kinase must interact with other gene products in the follicle cells to determine the dorsoventral fate of the follicle cells. We are currently analyzing genes that may act as downstream targets of the kinase in follicle cells. Eventually this should allow us to define in precise genetic and molecular terms how a dorsoventral signal is first produced in the germline during oogenesis, how this signal is transmitted from the germline to the overlying follicle cells, how it determines the fate of the follicle cells, and how the follicle cells, in turn, send a new signal to the germ cell that ultimately defines the dorsoventral pattern of the embryo.
A Gene Expression Screen in Identifies Novel JAK/STAT and EGFR Targets During Oogenesis. G3 (Bethesda). 2018 ;. .
A quantitative model of developmental RTK signaling. Dev Biol. 2018 ;. .
The Spatiotemporal Limits of Developmental Erk Signaling. Dev Cell. 2017 ;40(2):185-192. .
In vivo severity ranking of Ras pathway mutations associated with developmental disorders. Proc Natl Acad Sci U S A. 2017 ;114(3):510-515. .
Spatial organization of . Dev Biol. 2016 ;414(2):193-206. .
The Complexities and Unexpected Insights of Developmental Genetic Analysis. Curr Top Dev Biol. 2016 ;117:319-30. .
Dynamics of Inductive ERK Signaling in the Drosophila Embryo. Curr Biol. 2015 ;25(13):1784-90. .
Diversity of epithelial morphogenesis during eggshell formation in drosophilids. Development. 2015 ;142(11):1971-7. .
Repression of Gurken translation by a meiotic checkpoint in Drosophila oogenesis is suppressed by a reduction in the dose of eIF1A. Development. 2014 ;141(20):3910-21. .
Structure-activity relationships for a series of compounds that inhibit aggregation of the Alzheimer's peptide, Aβ42. Chem Biol Drug Des. 2014 ;84(5):505-12. .
Polarized deposition of basement membrane proteins depends on Phosphatidylinositol synthase and the levels of Phosphatidylinositol 4,5-bisphosphate. Proc Natl Acad Sci U S A. 2014 ;111(21):7689-94. .
Gertrud (Trudi) Schüpbach is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. She is a Howard Hughes Medical Institute Investigator and the Henry Fairfield Osborn Professor of Biology, Professor of Molecular Biology at Princeton University. She is also an adjunct faculty member of the Department of Biochemistry and Molecular Biology at the Robert Wood Johnson Medical School at Rutgers University. Schupbach received a Masters degree and a Ph.D. in Biology from the University of Zurich, Switzerland. She performed postdoctoral work first at the University of Zurich and later at Princeton University. She was appointed as a Research Biologist in the Department of Biology at Princeton University in 1985, and as Associate Professor in 1990 and was promoted to Full Professor in 1994. The research in her laboratory focuses on on cell to cell signaling processes that are involved in pattern formation during development, using Drosophila as a model system. In recent years the work has branched into questions of RNA localization and translational control, as well as understanding the general biology of epithelial cells. At Princeton, Professor Schupbach teaches both undergraduate and graduate courses and has guided many juniors and seniors in their thesis research.
Professor Schüpbach was elected to the European Molecular Biology Organization in 2000, and became a fellow of the American Association for the Advancement of Science in 2007. She received the Edwin F. Conklin Medal from the Society of Developmental Biology in 2006. She was confered a honorary Ph.D. degree from the University of Zurich, Switzerland in 2011. She served as the president of the Genetics Society of America in 2008, and as the president of the Drosophila board in 2000. She has been an associate editor of the journal Genetics for over two decades, and serves on the editorial board of PNAS, Developmental Cell and the Annual Review of Genetics. She has served on oversight, grant and award panels for the National Institute of Health, the National Science Foundation, the Keck Foundation, and the Damon Runyon Cancer Research Foundation. She has participated on advisory committees for Biology Departments at Carnegie Mellon University, Temple University, Johns Hopkins University, Ohio State University, and the European Molecular Biology Laboratory in Heidelberg, Germany. She is presently a member of the external advisory board of the Institute for Research in Biomedicine (IRB) in Barcelona, Spain.
- Honorary Degree, University of Zurich, Switzerland