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The scabrous (sea) gene encodes a secreted dimeric glycoprotein with putative coiled-coil domains N-terminally and a C-terminal region related to the blood clot protein fibrinogen. Homozygous sca mutants have extra bristle organs and rough eyes. We describe a GAL4-based expression system for testing rescue of the sea mutant phenotype by altered SCA proteins and for misexpression. We find that deletion of the fibrinogen-related domain (FReD) greatly decreases SCA function, confirming the importance of this conserved region. SCA function could not be restored by FReDs from human fibrinogen chain genes. However, proteins lacking any FReD still showed some function in both rescue and misexpression experiments, suggesting that putative effector-binding regions lie outside this domain. Consistent with this, proteins expressing only the FReD had no rescuing activity but were recessive negative; i.e., they enhanced the phenotype of sca mutations but had no phenotype in the presence of a wild-type sea allele. This suggests that the FReD contributes to SCA function by binding to other components of the bristle determination pathway, increasing the activity of the linked N-terminal region.

Mutations at the scabrous locus (sca) affect cell-cell signaling during neural development. Twenty-one mutant alleles of scabrous have been analyzed. Many synthesize no sca protein. In others, a defective protein is arrested intracellularly. Two mutants in which protein is not arrested must affect sca protein function outside the cell. Both affect the fibrinogen related domain (FReD), a 200-amino acid segment conserved in fibrinogen, tenascins, and other proteins. In fibrinogen, this region is involved in protein interactions and is altered in human mutations affecting blood clotting. In [sca.sup.UM2], an invariant Asp residue is replaced by Asn. In [sca.sup.MSKF], an insertion of the hobo transposable element truncates the sca protein at the start of the FReD. The [sca.sup.MSKF] allele has dominant negative properties, indicating that the truncated amino-terminal portion interferes with the function of some other gene product. These mutations show that the conserved FReD is essential for wild-type sca function, but suggest that the amino-terminal domain 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.