The aim of this project is the analysis how spatial asymmetries arise in the developing egg chamber of Drosophila melanogaster. We have shown that a signalling process between the germline and the overlying follicle cells establishes the dorso-ventral pattern of both the egg shell and the embryo. We found that torpedo, a central gene in this cell communication pathway, encodes the Drosophila homolog of the vertebrate Epidermal Growth Factor receptor (EGFr). We will analyze at the molecular level a set of 32 torpedo alleles which differentially affect receptor function in different cell types. To analyze the upstream germline processes involved in torpedo activation we propose a detailed genetic and molecular analysis of the gene cornichon which is presently our best candidate for encoding a ligand of the receptor. We will subsequently analyze the interactions between cornichon and gurken, fs(1)K10, capuccino, and spire, genes that also act in the germline and are involved in ligand production. This will allow us to describe the pathway of temporal and spatial control used by the system for ligand production. We will analyze the two cellular response pathways that are activated by the torpedo receptor: the establishment of dorsal follicle cell fates and the regulation of a new, ventralizing signal which is produced in the follicle cells and transmitted back to the embryo. We have identified a candidate class of genes for the first response pathway. We propose to analyze this class and identify genes that promote the establishment of dorsal follicle cell fates. We have also identified a gene (windbeutel) that acts in the second pathway and participates in the production of a new signal in the follicle cells which ultimately established embryonic cell fates. Genetic and molecular techniques will be used to analyze windbeutel. In addition, a search for additional genes that act in the torpedo pathway will be performed by screening for enhancer or suppressor mutations. We will also analyze mutations that affect early events in egg chamber patterning. This will provide information about the primary mechanisms that are used in Drosophila to establish the initial anterior-posterior and dorso-ventral asymmetries. The proposed research will allow us to determine how a spatially and temporally controlled activation of the torpedo receptor tyrosine kinase is achieved in development, and provide a detailed understanding of the different developmental pathways that are controlled by receptor activation. Excellent biochemical data on the mode of action of such receptors has been obtained using vertebrate tissue culture systems. Our studies in the egg chamber of Drosophila will complement such analyses, and yield insights into the role of such receptors in the developing organism.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM040558-06
Application #
3298229
Study Section
Genetics Study Section (GEN)
Project Start
1988-09-01
Project End
1995-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Princeton University
Department
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Neuman-Silberberg, F S; Schupbach, T (1996) The Drosophila TGF-alpha-like protein Gurken: expression and cellular localization during Drosophila oogenesis. Mech Dev 59:105-13
Hawkins, N C; Thorpe, J; Schupbach, T (1996) Encore, a gene required for the regulation of germ line mitosis and oocyte differentiation during Drosophila oogenesis. Development 122:281-90
Roth, S; Neuman-Silberberg, F S; Barcelo, G et al. (1995) cornichon and the EGF receptor signaling process are necessary for both anterior-posterior and dorsal-ventral pattern formation in Drosophila. Cell 81:967-78
Clifford, R; Schupbach, T (1994) Molecular analysis of the Drosophila EGF receptor homolog reveals that several genetically defined classes of alleles cluster in subdomains of the receptor protein. Genetics 137:531-50
Roth, S; Schupbach, T (1994) The relationship between ovarian and embryonic dorsoventral patterning in Drosophila. Development 120:2245-57
Neuman-Silberberg, F S; Schupbach, T (1994) Dorsoventral axis formation in Drosophila depends on the correct dosage of the gene gurken. Development 120:2457-63
Neuman-Silberberg, F S; 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
Clifford, R; Schupbach, T (1992) The torpedo (DER) receptor tyrosine kinase is required at multiple times during Drosophila embryogenesis. Development 115:853-72
Schupbach, T; Wieschaus, E (1991) Female sterile mutations on the second chromosome of Drosophila melanogaster. II. Mutations blocking oogenesis or altering egg morphology. Genetics 129:1119-36
Manseau, L J; Schupbach, T (1989) cappuccino and spire: two unique maternal-effect loci required for both the anteroposterior and dorsoventral patterns of the Drosophila embryo. Genes Dev 3:1437-52

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