Receptor tyrosine kinases (RTK) are key molecules controlling cell growth and differentiation, and mutations in major RTKs and their targets have been implicated in certain forms of cancer. We investigate the mechanisms involved in the activation of the Drosophila homolog of the Epidermal Growth Factor receptor (Egfr) during oogenesis, and the cellular responses pathways activated in the follicle cells. We focus on our recent finding that activation of the receptor in oogenesis is regulated by the meiotic cell cycle via a checkpoint kinase. We also investigate how activity of Egfr regulates major developmental events in the follicle cells, resulting in the patterning of egg shell and embryo. Three major goals: (1) Analysis of the meiotic checkpoint mechanism that regulates Gurken (Grk) production. We will perform genetic tests of candidate mutations, screen for new mutations that may act in conjunction with the checkpoint kinase Kei-41, and determine whether they act in conjunction with the checkpoint kinase Mei-41 and determine whether they act in the process that couples the DNA repair sensing mechanism in meiosis to events in the oocyte cytoplasm. (2) Translational regulation of grk RNA. We will determine how the meiotic checkpoint regulates translation of grk. We will also investigate checkpoint independent, parallel pathways of translational regulation of grk. We have found a gene, encore, which affects Grk protein accumulation. Encore and other candidates will be tested for genetic physical interactions with the known translational regulators of grk RNA. (3) Analysis of the response pathways acting in the follicle cells of the ovary. We will focus on the three cellular responses that depend on Egfr activation in the follicle cells. We will identify and analyze new target genes acting downstream in these processes using either microarray techniques, or a mosaic follicle cell system. We will continue with the analysis of the Drosophila homolog of the Cb1 oncogene. In collaboration with Wieschaus we will analyze interactions of Egfr with the Armadillo/beta catenin pathway in follicle cells.
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