MOLECULAR ANALYSIS OF SCABROUS MUTANT ALLELES FROM DROSOPHILA-MELANOGASTER INDICATES A SECRETED PROTEIN WITH 2 FUNCTIONAL DOMAINS

Mutations at the scabrous locus (sca) affect cell-cell signaling durin g neural developent. Twenty-one mutant alleles of scabrous have been a nalyzed. Many synthesize no sca protein. In others, a defective protei n is arrested intracellularly. Two mutants in which protein is not arr ested must affect sca protein function outside the cell. Both affect t he fibrinogen related domain (FReD), a 200-amino acid segment conserve d in fibrinogen, tenascins, and other proteins. In fibrinogen, this re gion is involved in protein interactions and is altered in human mutat ions affecting blood clotting. In sca(UM2), an invariant Asp residue i s replaced by Asn. In sca(MSKF) an insertion of the hobo transposable element truncates the sca protein at the start of the FReD. The sca(MS KF) allele has dominant negative properties, indicating that the trunc ated amino-terminal portion interferes with the function of some other gene product. These mutations show that the conserved FReD is essenti al for wild-type scn function, but suggest that the amino-terminal dom ain also interacts with other proteins. Genetic interactions identify the neurogenic genes Notch and Delta as potential interacting proteins , but other neural mutations were without effect. Models for the role of a two-domain protein in neural development are discussed.