A Screen to Identify Genes that Interact with Abl Tyrosine Kinase in Drosophila. Selena Washington, Traci L. Stevens. Biology, Randolph-Macon College, Ashland, VA.

   Actin filaments are highly dynamic, thin polymers found throughout eukaryotic cells. Actin is highly concentrated in the cortex, where it directs cell movement and shape. The tyrosine kinase Abl regulates cell morphogenesis by directing the organization of the actin cytoskeleton. In cell culture, expression of an activated form of Abl, Bcr-Abl, alters actin structures and cell migration, and in Drosophila, expression of Bcr-Abl disrupts processes that require regulated cell migration, such as dorsal closure and head involution. In order to identify components of Abl signaling pathways that regulate cell migration, our laboratory is conducting a genetic screen that has identified mutant alleles of several genes that modify phenotypes associated with Bcr-Abl expression. Here, we tested these interacting mutations in an abl loss-of-function background in order to provide additional evidence of a relationship with wild-type abl. First, we used embryos that lack maternal Abl but receive a wild-type copy of abl paternally. These abl mutant embryos are viable; however, heterozygous mutations of abi or garz, two genes that modify phenotypes associated with Bcr-Abl expression, resulted in lethality, providing more general support for a role of the products of these genes in normal Abl signaling pathways. Mutant alleles of all other Bcr-Abl interacting genes, however, did not affect the phenotypes of abl mutant embryos; therefore, we increased the sensitivity of this assay by removing the paternal copy of abl. Embryos that lack both maternal and zygotic Abl die with defects in epithelial morphogenesis. Thus far, we have tested mutant alleles of two genes that modify Bcr-Abl dependent phenotypes, Khc and garz, and found that heterozygous mutations in either enhanced the defects of embryos lacking maternal and zygotic Abl. These results suggest that this may be a more sensitive background in which to detect interactions with loss-of-function abl and provide additional support for a relationship between wild-type Abl and the products of Khc and garz in cell migration.