HEXIM knockdown triggers apoptosis-induced proliferation and deregulates Hedgehog signaling

We address the function of HEXIM, an inhibitor of the general transcriptional elongation regulator P-TEFb which regulates the transcriptional status of many developmental genes, during Drosophila development. We showed that HEXIM knockdown mutants display organs development failure. In the wing disc, it induces apoptosis and affects Hh signaling. The continuous death of proliferative cells is compensated by apoptosis-induced cell proliferation, in a manner similar to that of differentiated cells, together with high levels of Hh and Ci. We completed this analysis with microarrays to characterize the molecular phenotype of HEXIM knockdown during eye differentiation. HEXIM knockdown during eye differentiation was carried out with a UAS-Hexim-RNAi strain crossed with a GMR-Gal4 driver strain (Bloomington stock center)). Adult GMR>RNAi Hexim flies display slightly smaller, rough and often necrosed eyes. Total RNA were collected from isolated heads. We then used microarray to compare the transcriptome of HEXIM knockdown mutant with that of wild type flies.