Faculty & Research

Molecular Biology Faculty

Gertrud M. Schüpbach

Henry Fairfield Osborn Professor of Biology
Professor of Molecular Biology

Gertrud Schupbach

Phone (609) 258-1365
locationMoffet Lab, 428
Phone Lab (609) 258-6492
Faculty Assistant
Laisa Eimont
Phone (609) 258-2933


Research Focus

Genetic 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.

Selected Publications

Lim B, Dsilva CJ, ... Schüpbach T, Kevrekidis IG, Shvartsman SY. (2015) Dynamics of Inductive ERK Signaling in the Drosophila Embryo. Curr Biol.25(13):1784-90. [Epub ahead of print]

Osterfield M, Schüpbach T, Wieschaus E, Shvartsman SY. (2015) Diversity of epithelial morphogenesis during eggshell formation in drosophilids.  Development. 142: 1971-7. Pubmed

Li W, Klovstad M, Schüpbach T. (2014) Repression of Gurken translation by a meiotic checkpoint in Drosophila oogenesis is suppressed by a reduction in the dose of eIF1A. Development. 141: 3910-21. Pubmed

Devergne O, Tsung K, Barcelo G, Schüpbach T. (2014) Polarized deposition of basement membrane proteins depends on Phosphatidylinositol synthase and the levels of Phosphatidylinositol 4,5-bisphosphate. Proc Natl Acad Sci. 111: 7689-94. Pubmed

McKoy AF, Chen J, Schupbach T, Hecht MH. (2014) Structure activity relationships for a series of compounds that inhibit aggregation of the Alzheimer's peptide, Aβ42. Chem Biol Drug Des. 84: 505-12. Pubmed

Domanitskaya E, Anllo L, Schüpbach T. (2014) Phantom, a cytochrome P450 enzyme essential for ecdysone biosynthesis, plays a critical role in the control of border cell migration in Drosophila. Dev Biol. 386: 408-18. Pubmed

Fontenele M, Lim B, Oliveira D,...Schupbach T, Araujo H. (2013) Calpain A modulates Toll responses by limited Cactus/IκB proteolysis. Mol Biol Cell. 24: 2966-80. Pubmed

Osterfield M, Du X, Schüpbach T, Wieschaus E, Shvartsman SY. (2013) Three-dimensional epithelial morphogenesis in the developing Drosophila egg. Dev Cell. 24: 400-10. Pubmed

McKoy AF, Chen J, Schupbach T, Hecht MH. (2012) A novel inhibitor of Aβ peptide aggregation: from high throughput screening to efficacy in an animal model for Alzheimer's disease. J Biol Chem. 287: 38992-9000. Pubmed

Ferguson SB, Blundon MA, Klovstad MS, Schüpbach T. (2012) Modulation of gurken translation by insulin and TOR signaling in Drosophila. J Cell Sci. 125: 1407-19. Pubmed

Domanitskaya E, Schüpbach T. (2012) CoREST acts as a positive regulator of Notch signaling in the follicle cells of Drosophila melanogaster. J Cell Sci. 125: 399-410. PubMed

Pane A, Jiang P, Zhao DY, Singh M, Schüpbach T. (2011) The Cutoff protein regulates piRNA cluster expression and piRNA production in the Drosophila germline. EMBO J. 30: 4601-15. Pubmed

Cheung LS, Schüpbach T, Shvartsman SY. (2011) Pattern formation by receptor tyrosine kinases: analysis of the Gurken gradient in Drosophila oogenesis. Curr Opin Genet Dev. 21: 719-25. PubMed

Sun Y, Yan Y, Denef N, Schüpbach T. (2011) Regulation of somatic myosin activity by Protein Phosphatase 1{beta} controls Drosophila oocyte polarization. Development. 138: 1991-2001 PubMed

Yan Y, Denef N, Tang C, Schüpbach T. (2011) Drosophila PI4KIIIalpha is required in follicle cells for oocyte polarization and Hippo signaling. Development. 138: 1697-703. PubMed

Sethi N, Yan Y, Quek D, Schupbach T, Kang Y. (2010) Rabconnectin-3 is a functional regulator of mammalian notch signaling. J Biol Chem. 285: 34757-64. PubMed

Yan Y, Denef N, Schüpbach T. (2009) The vacuolar proton pump, V-ATPase, is required for notch signaling and endosomal trafficking in Drosophila. Dev Cell. 17: 387-402. PubMed

Schüpbach T. (2009) Developmental biology: Pipe's smoking guns. Curr Biol. 19: R548-550. PubMed

Yakoby N, Bristow CA, Gong D,...Schupbach T, Shvartsman S. (2008) A combinatorial code for pattern formation in Drosophila oogenesis. Dev Cell 15: 725-37. PubMed

Jaramillo AM, Weil TT, Goodhouse J, Gavis ER, Schupbach T. (2008) The dynamics of fluorescently labeled endogenous gurken mRNA in Drosophila. J Cell Sci. 121: 887-94. PubMed

Klovstad M, Abdu U, Schüpbach T. (2008) Drosophila brca2 is required for mitotic and meiotic DNA repair and efficient activation of the meiotic recombination checkpoint. PLoS Genet.4: e31. PubMed

Denef N, Chen Y, Weeks SD, Barcelo G, Schüpbach T. (2008) Crag regulates epithelial architecture and polarized deposition of basement membrane proteins in Drosophila. Dev Cell. 14: 354-64. PubMed

Yakoby N, Lembong J, Schüpbach T, Shvartsman SY. (2008) Drosophila eggshell is patterned by sequential action of feedforward and feedback loops. Development. 135: 343-51. PubMed

Clouse KN, Ferguson SB, Schüpbach T. (2008) Squid, Cup, and PABP55B function together to regulate gurken translation in Drosophila. Dev Biol. 313: 713-24. PubMed

Pane A, Wehr K, Schüpbach T. (2007) zucchini and squash encode two putative nucleases required for rasiRNA production in the Drosophila germline. Dev Cell. 12: 851-62. PubMed

Swan A, Schupbach T. (2007) The Cdc20 (Fzy)/Cdh1-related protein, Cort, cooperates with Fzy in cyclin destruction and anaphase progression in meiosis I and II in Drosophila. Development. 134: 891-99. PubMed

Chen Y, Pane A, Schupbach T. (2007) Cutoff and aubergine mutations result in retrotransposon upregulation and checkpoint activation in Drosophila. Curr Biol. 17: 637-42. PubMed

Goentoro LA, Reeves GT, Kowal CP, Martinelli L, Schupbach T, Shvartsman SY. (2006) Quantifying the Gurken morphogen gradient in Drosophila oogenesis. Dev Cell. 11: 263-72. PubMed

Chen Y, Schupbach T. (2006) The role of brinker in eggshell patterning. Mech Dev. 123: 395-406. PubMed

Wehr K, Swan A, Schupbach T. (2006) Deadlock, a novel protein of Drosophila, is required for germline maintenance, fusome morphogenesis and axial patterning in oogenesis and associates with centrosomes in the early embryo. Dev Biol. 294: 406-17. PubMed

Abdu U, Bar D, Schupbach T. (2006) spn-F encodes a novel protein that is involved in the organization of specialized microtubule networks in Drosophila. Development. 133: 1477-84. PubMed

Swan A, Barcelo G, Schupbach T. (2005) Drosophila Cks30A interacts with Cdk1 to target Cyclin A for destruction in the female germline. Development. 132: 3669-78. PubMed

Swan A, Schupbach T. (2005) Drosophila female meiosis and embryonic syncytial mitosis use specialized Cks and CDC20 proteins for cyclin destruction. Cell Cycle. 4: 1332-34. PubMed

Murthy M, Ranjan R, Denef N, Higashi ME, Schupbach T, Schwarz TL. (2005) Sec6 mutations and the Drosophila exocyst complex. J Cell Sci. 118: 1139-50. PubMed

Goodrich JS, Clouse KN, Schupbach T. (2004) Hrb27C, Sqd and Otu cooperatively regulate gurken RNA localization and mediate nurse cell chromosome dispersion in Drosophila oogenesis. Development. 131: 1949-58. PubMed

Ohlmeyer JT, Schupbach T. (2003) Encore facilitates SCF-Ubiquitin-proteasome-dependent proteolysis during Drosophila oogenesis. Development. 130: 6339-49. PubMed

Gupta T, Schupbach T. (2003) Cct1, a phosphatidylcholine biosynthesis enzyme, is required for Drosophila oogenesis and ovarian morphogenesis. Development. 130: 6075-87. PubMed

Van Buskirk C, Schupbach T. (2002) Half pint regulates alternative splice site selection in Drosophila. Dev Cell. 2: 343-53. PubMed

Abdu U, Brodsky M, Schupbach T. (2002) Activation of a meiotic checkpoint during Drosophila oogenesis regulates the translation of Gurken through Chk2/Mnk. Curr Biol. 12: 1645-51. PubMed

Pai LM, Barcelo G, Schupbach T. (2000) D-cbl, a negative regulator of the Egfr pathway, is required for dorsoventral patterning in Drosophila oogenesis. Cell. 103: 51-61. PubMed

Norvell A, Kelley RL, Wehr K, Schupbach T. (1999) Specific isoforms of squid, a Drosophila hnRNP, perform distinct roles in Gurken localization during oogenesis. Genes Dev. 13: 864-76. PubMed

Nilson LA, Schupbach T. (1998) Localized requirements for windbeutel and pipe reveal a dorsoventral prepattern within the follicular epithelium of the Drosophila ovary. Cell. 93: 253-62. PubMed

Neuman-Silberberg FS, Schupbach T. (1993) The Drosophila dorsoventral patterning gene gurken produces a dorsally localized RNA and encodes a TGF alpha-like protein. Cell. 75: 165-74. PubMed

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