Phenotypic Characterization Of Drosophila Tumor Suppressor Gene Lgl Mutant In Developing Larvae And Understanding The Role Of JNK Activation In Lgl Mutation-Induced Phenotypes

As one of the neoplastic tumor suppressor genes (nTSGs), Drosophila lethal giant larvae(lgl) plays a critical role in the control of cell polarity and proliferation. To uncover the molecuLar mechanisms underlying lgl mutation-induced tumor growth, we used cell number counting and immunofluorescence staining to dynamically characterize the phenotypes of lgl mutation in developing larvae. We show that lgl mutant imaginal discs exhibit an abnormal developmental pattern. Mutant wing imaginal discs are much smaller when compared to similarly aged wild-type discs during normal developmental stage (5 days after egg laying). Only during the extended larval life, the mutant discs actually overgrow. Importantly, loss of cell polarity occurs prior to overgrowth, which implies some causative contribution of polarity defects to neoplastic tumor growth. In addition, lgl mutation triggers caspase-dependent apoptosis, especially during early larval stages. We also show that JNK is highly activated in lgl mutant wing discs. Using UAS-Gal4 system to overexpress bskDN to suppress JNK activation, we show that the developmental pattern of lgl mutant is partly rescued. The mutant larvae do not enter an extended third instar stage. Normal cell polarity and wing disc morphology are partially restored in lgl mutant discs. Furthermore, the overgrowth and caspase-dependent apoptosis are completely blocked. Thus, JNK activation is required for the phenotypes induced by lgl mutation.