A screen for abl-interacting genes in axon pathfinding. J. Rusch ¹, K. Sheard ¹, M.M. Emerson ², D.L. Van Vactor ^1,2. 1) Dept Cell Biology, Harvard Medical School, Boston, MA; 2) Program in Neuroscience, Harvard Medical School, Boston, MA.

   The abl tyrosine kinase plays an important role in the pathfinding of certain axons in the embryonic Drosophila nervous system, where it has been shown to function in the Dlar receptor tyrosine phosphatase pathway. abl loss-of-function mutants display premature stalling of growth cones in a subset of motor neurons, including ISNb, as well as third fascicle breaks in the midline, and midline crossing. Conversely, overexpression of abl leads to a 'bypass' phenotype where ISNb fails to innervate its correct targets and instead follows ISN toward more dorsal targets, and to midline crossing. We performed a screen for genes interacting with abl in this process using the Rørth EP line collection, initially screening for a modification of a kinase dependent rough eye phenotype caused by abl overexpression in the developing eye. EPs found to score positive in this screen were then tested for their modification of the abl overexpression phenotype in the developing nervous system by co-overexpressing the EP and abl under elav-GAL4 control. On the third chromosome we identified 5 enhancers of abl overexpression in which the percentage of segments showing bypass phenotypes was increased.
   One of the interactors corresponds to the Drosophila homolog of the fragile-X mental retardation gene 1, dfmr1. In vertebrates, FMRP has been shown to be an RNA binding protein which binds to approximately 4% of RNAs expressesd in the brain, including its own message. FMRP associates with actively translating polyribosomes in an RNA dependent manner via mRNPs. In vitro studies also suggest that FMRP may suppress translation of the RNAs it binds.