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Genetic screens for dominant second-site mutations that suppress the lethality of Abl mutations in Drosophila identified alleles of only one gene, enabled (ena). We report that the ena protein contains proline-rich motifs and binds to Abl and Src SH3 domains, ena is also a substrate for the Abl kinase; tyrosine phosphorylation of ena is increased when it is coexpressed in cells with human or Drosophila Abl and endogenous ena tyrosine phosphorylation is reduced in Abl mutant animals. Like Abl, ena is expressed at highest levels in the axons of the embryonic nervous system and ena mutant embryos have defects in axonal architecture. We conclude that a critical function of Drosophila Abl is to phosphorylate and negatively regulate ena protein during neural development.

In the absence of the Drosophila abl protein-tyrosine kinase (PTK), loss-of-function mutations in either disabled or prospero have dominant phenotypic effects on embryonic development. Molecular and genetic characterizations indicate that the products of these genes interact with the abl PTK by different mechanisms. The interaction between abl and prospero, which encodes a nuclear protein required for correct axonal outgrowth, is likely to be indirect. In contrast, the product of disabled may be a substrate for the abl PTK. The disabled protein is colocalized with abl in axons, its predicted amino acid sequence contains 10 motifs similar to the major autophosphorylation site of abl, and the protein is recognized by antibodies to phosphotyrosine.

The pattern of structures on most of the adult cuticle of Drosophila is determined in the larval imaginal disks. The Drosophila growth factor homolog decapentaplegic (dpp) is believed to participate in pattern formation in imaginal disks, primarily along what will become the proximal-to-distal axis of adult appendages. We report that dpp expression in wing, leg, and eye-antennal imaginal disks is localized to a band of cells along the presumptive proximal-to-distal axis. The pattern and level of dpp expression in imaginal disks is affected by mutant lesions that remove 3' cis-regulatory sequences. We demonstrate that one portion of the 3' cis-regulatory region contains regulatory elements sufficient to activate gene expression in a subset of the cells that normally express dpp in the imaginal disks, allowing rescue of dpp mutant phenotypes. We propose that the complete dpp expression pattern is generated by an array of 3' regulatory elements that differ in their potency in specific disks and in certain positions within a disk. The identification of the factors that activate these elements should provide clues as to how positional information is encoded in imaginal disks.

The decapentaplegic (dpp) locus of Drosophila melanogaster is a greater than 55 kb genetic unit required for proper pattern formation during the embryonic and imaginal development of the organism. We have proposed that these morphogenetic functions result from the action of a secreted transforming growth factor-beta (TGF-beta)-related protein product encoded by dpp. In this paper we localize 60 mutations on the molecular map of dpp. The positions of these mutations cluster according to phenotypic class, identifying the locations of specific dpp functions. By Northern and cDNA analysis, we characterize five overlapping dpp transcripts. On the basis of the locations of the overlaps relative to a previously sequenced cDNA, it is likely that these transcripts all encode similar or identical polypeptides. We propose that the bulk of dpp DNA consists of extensive arrays of cis-regulatory information. The large (greater than 25-kb) 3' cis-regulatory region represents a novel feature of dpp gene organization

Mutant alleles of the Drosophila decapentaplegic (dpp) gene affect embryonic dorsal-ventral pattern formation, larval viability, and adult cuticle formation from the imaginal disks. The dpp DNA required for this array of functions spans almost 50 kb. We report that the embryonic lethal, ventralizing alleles of the dpp gene are rescued in transgenic animals by an 8-kb fragment of the wild-type dpp DNA. Full rescue, from embryonic lethality to adult viability, is obtained in two situations: in animals hemizygous for the haplolethal dpp gene, and in animals hemizygous for either of two recessive embryonic lethal alleles. In embryos null for dpp, the transformation of dorsal cuticle to ventral cuticle is blocked by one copy of the dpp transposon; two copies permit the hatching of the larvae. The portion of dpp sufficient for these embryonic functions encodes a protein with homology to the transforming growth factor-beta (TGF-beta) family of proteins (Padgett et al. 1987). The larval and imaginal disk functions of dpp are not rescued by the 8-kb portion of the gene and must require additional sequences from the 50 kb of DNA.