Identification of Nanos and Pumilio Targets in Drosophila melanogaster Class IV Dendritic Arborization Neurons

Abstract

The morphogenesis of dendritic arbors determines how well neurons can sense and respond to external stimuli, and defects in dendritic morphogenesis are associated with many human neurological diseases. The dendritic arborization (da) neurons, sensory neurons in the Drosophila larvae, have been important for identifying factors that contribute to proper dendritic morphogenesis. The translational regulators Nanos (Nos) and Pumilio (Pum) are required to maintain dendritic complexity of the extensively branched class IV da neurons in third instar larvae. Studies in our lab suggest that the defects associated with both nos- and pum-deficient da neurons are partially due to derepression of head involution defective (hid), a proapoptotic factor. We hypothesize that if hid is a target of Nos- and Pum-mediated repression, overexpression of Hid in an otherwise wild-type background should recapitulate the nos mutant phenotype. Overexpression of Hid recapitulated the nos mutant phenotype, indicating that the morphological defects in nos- and pum-deficient neurons are due to increased levels of Hid. However, depression of Hid does not account for all of the phenotypes observed in nos- and pum-deficient neurons, suggesting that there are other downstream targets of Nos and Pum in class IV da neurons. In order to identify these targets, we performed a genetic suppression screen using a series of deficiencies spanning the second chromosome. We identified six deficiencies that suppressed the nos mutant phenotype and six deficiencies that enhanced the nos mutant phenotype. These deficiencies will be analyzed to determine which genes within the larger deficiencies are potentially being targeted by Nos and Pum.