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 s evere rough eye phenotype from similar to 500 fly lines, each harborin g a single autosomal insertion of a P element (Bm Delta w). Excision o f 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 reco mbination, 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 con spicuous wing phenotypes such as a notched blade and the loss of a cro ss vein. The sequence of cno cDNA clones isolated from an embryonic cD NA library revealed a long open reading frame that potentially encodes a 1893-amino-acid protein with the GLGF/DHR motif, a conserved sequen ce in Discs large, Dishevelled, and some other proteins associated wit h 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) dou ble mutant flies also exhibit a ''giant socket'' phenotype. These phen otypes 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 formati on of extra wing veins in cno(mis1) homozygotes. The genetic interacti ons suggest that cno participates with members of the N pathway in reg ulating adhesive cell-cell interactions for the determination of cell fate.