CANOE ENCODES A NOVEL PROTEIN CONTAINING A GLGF/DHR MOTIF AND FUNCTIONS WITH NOTCH AND SCABROUS IN COMMON DEVELOPMENTAL PATHWAYS IN DROSOPHILA

The canoe(misty1) (cno(mis1)) mutation was isolated by virtue of its severe rough eye phenotype from similar to 500 fly lines, each harboring a single autosomal insertion of a P element (Bm Delta w). Excision of the P element generated a lethal, null allele, cno(mis10), together with many revertants with normal eye morphology. Ommatidia homozygous for cno(mis10), produced in an otherwise wild-type eye by somatic recombination, typically contain a reduced number of outer photoreceptors. Some cno(mis1) homozygous adults bear extra macrochaetes on the head, notum, humerus and/or scutellum. cno(mis1) hemizygotes often show conspicuous wing phenotypes such as a notched blade and the loss of a cross vein. The sequence of cno cDNA clones isolated from an embryonic cDNA library revealed a long open reading frame that potentially encodes a 1893-amino-acid protein with the GLGF/DHR motif, a conserved sequence in Discs large, Dishevelled, and some other proteins associated with cellular junctions. Flies doubly mutant for cno(mis1) and scabrous(1) (sca(1)) and those for cno(mis1) and the split (spl) allele of Notch (N) always have rumpled wings curved downward. The spl; cno(mis1) double mutant flies also exhibit a ''giant socket'' phenotype. These phenotypes are rarely observed in flies singly mutant for either cno(mis1), sca(1) or spl. The wing vein gaps caused by Abruptex(1), a N allele producing an activated form of N protein, are dominantly suppressed by cno(mis1). Heterozygosity for shaggy and myospheroid promotes formation of extra wing veins in cno(mis1) homozygotes. The genetic interactions suggest that cno participates with members of the N pathway in regulating adhesive cell-cell interactions for the determination of cell fate.