THE DROSOPHILA-MELANOGASTER FLIGHTLESS-I GENE INVOLVED IN GASTRULATION AND MUSCLE DEGENERATION ENCODES GELSOLIN-LIKE AND LEUCINE-RICH REPEAT DOMAINS AND IS CONSERVED IN CAENORHABDITIS-ELEGANS AND HUMANS

Mutations at the flightless-I locus (fliI) of Drosophila melanogaster cause flightlessness or, when severe, incomplete cellularization durin g early embryogenesis, with subsequent abnormalities in mesoderm invag ination and in gastrulation. After chromosome walking, deficiency mapp ing, and transgenic analysis, we have isolated and characterized fligh tless-I cDNAs, enabling prediction of the complete amino acid sequence of the 1256-residue protein. Data base searches revealed a homologous gene in Caenorhabditis elegans, and we have isolated and characterize d corresponding cDNAs. By using the polymerase chain reaction with nes ted sets of degenerate oligonucleotide primers based on conserved regi ons of the C. elegans and D. melanogaster proteins, we have cloned a h omologous human cDNA. The predicted C. elegans and human proteins are, respectively, 49% and 58% identical to the D. melanogaster protein. T he predicted proteins have significant sequence similarity to the acti n-binding protein gelsolin and related proteins and, in addition, have an N-terminal domain consisting of a repetitive amphipathic leucine-r ich motif. This repeat is found in D. melanogaster, Saccharomyces cere visiae, and mammalian proteins known to be involved in cell adhesion a nd in binding to other proteins. The structure of the maternally expre ssed flightless-I protein suggests that it may play a key role in embr yonic cellularization by interacting with both the cytoskeleton and ot her cellular components. The presence of a highly conserved homologue in nematodes, flies, and humans is indicative of a fundamental role fo r this protein in many metazoans.