GENETIC CONTROL OF CELL FATE DIVERSITY IN DROSOPHILA

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This proposal explores the mechanisms by which Wingless (Wg) signaling promotes cell fate decisions in the Drosophila embryonic epidermis. Wg and its vertebrate Wnt homologues are essential for generating pattern in both invertebrate and vertebrate embryos. Inappropriate activation of the Wnt signaling pathway has been implicated in mammary tumors in mice, and melanomas and colon carcinomas in humans. Therefore, understanding how these molecules influence cell fate decisions is relevant to both fetal and adult human health issues. The project utilizes the easily scored larval pattern as an assay system for Wg-mediated cellular decisions. Drosophila embryos secrete a tough cuticular layer that displays a rich pattern of structures, indicative of discrete cell identities in the underlying epidermis. Wg signaling is required for generating the diverse array of cuticular structures observed in the wild- type animal. Aim 1 of this proposal discusses a mutant Wg molecule that specifies some, but not all, of the cell fates normally found in wild-type pattern. The biochemical basis for this limited signaling activity will be examined with respect to putative Wg receptor molecules and processing steps known to be essential for Wg function. Aim 2 tests other components of the Wg signal transduction cascade to determine their precise roles in the distinct Wg-mediated cell fate decisions. Germ line clone analysis of the recently identified transcription factor, dTCF, will be undertaken to determine whether the subtle effects of its zygotic loss are due to maternal contribution, or reflect participation in only a subset of the Wg-mediated cellular responses. Aim 3 examines other genes that influence the diversity of cell fates specified by Wg activity, particularly concentrating on a newly identified gene that specifically influences the diversity generated by the mutant Wg molecule described in Aim 1. This specificity may indicate a novel function in the Wg pathway. Aim 4 describes a plan for the molecular cloning of this new gene and for the subsequent characterization of its gene product.