MOLECULAR ANALYSIS OF EMS-INDUCED FRIZZLED MUTATIONS IN DROSOPHILA-MELANOGASTER

The frizzled (fi) gene of Drosophila is essential for the development of normal tissue polarity in the adult cuticle of Drosophila. In fz mu tants the parallel array of hairs and bristles that decorate the cutic le is disrupted. Previous studies have shown that fi encodes a membran e protein with seven putative transmembrane domains, and that it has a complex role in the development of tissue polarity, as there exist bo th cell-autonomous and cell nonautonomous alleles. We hare now examine d a larger number of alleles and found that 15 of 19 alleles display c ell nonautonomy. We have examined these and other alleles by Western b lot analysis and found that most fz mutations result in altered amount s of Fz protein, and many also result in a Fz protein that migrates ab errantly in SDS-PAGE. We have sequenced a subset of these alleles. Cel l nonautonomous fi alleles were found to be associated with mutations that altered amino acids in all regions of the Fz protein. Notably, th e four cell-autonomous mutations were all in a proline residue located in the presumptive first cytoplasmic loop of the protein. We have als o cloned and sequenced the St gene from D. virilis. Conceptual transla tion of the D. virilis open reading frame indicates that the Fz protei n is unusually well conserved. Indeed, in the putative cytoplasmic dom ains the Fz proteins of the two species are identical.