Many basic insights into the mechanisms of human disease and development have come from experiments using Drosophila as a model system. Patterning of the Drosophila egg begins in the ovarian egg chamber. The gurken-Egfr signaling pathway is required to successively define the anterior-posterior and dorsal-ventral axes. During early oogenesis, Gurken in the oocyte activates Egfr in adjacent terminal follicle cells to specify a posterior fate. This oocyte-to-follicle cell signaling by Gurken is followed by an unidentified signal back to the oocyte from the posterior follicle cells, which causes reorganization of the microtubule organizing center. This signaling results in the localization of the maternal bicoid and oskar transcripts to opposite poles of the oocyte to define anterior-posterior asymmetry. Proper anterior-posterior axis formation requires the fettucine (fet) gene, which encodes an HMG box transcription factor. Embryos produced by mutant fet females develop with a bicaudal phenotype, in which the anterior is replaced by a mirror-image duplication of the posterior. Mosaic analysis indicates that fet s required in the follicle cells. Yet, preliminary results indicate that bicoid and oskar mRNA are properly localized within the oocyte, arguing that fet is not involved in regulating the signal controlling microtubule polarity. Together, these observations suggest the existence of a novel follicle cell-to-oocyte signal that is hypothesized to regulate translation of oskar mRNA in the posterior. The overall objective of this proposal is to understand how fet action in follicle cells helps establish anterior-posterior polarity of the embryo. The DNA sequences encoding fet function will be defined, and the spatial expression of fet transcripts and Fet protein within the follicular epithelium will be investigated. The oocyte in mutant egg chambers will be further characterized with molecular probes; specific models that hypothesize fet involvement in the translational regulation of oskar mRNA will be tested. Finally, genetic screens aimed at identifying other components of the hypothesized signaling pathway will be carried out. An enduring problem in biology is understanding how an egg generates pattern along its body axes. The proposed experiments are aimed at characterizing how a particular gene called fettucine, which is conserved in humans, controls proper head-to-tail development in the fruit fly egg. ? ?
