Date of Publication :17th May 2018

Abstract: Hippo signalling has emerged as a novel tumor suppressor pathway that plays an important role in the regulation of tissue and organ size during development. The Hippo pathway consists of a core kinase cascade in which Hpo phosphorylates the protein kinase Warts. Activated Wts then go and phosphorylate and inactivate the transcriptional coactivator Yorkie (Yki). Wts promotes the association of Yki with 14-3-3 proteins, which helps anchor Yki in the cytoplasm and prevent its transport to the nucleus. Homothorax -a homeodomain transcription factor- in conjunction with Yki has been shown to regulate micro RNA bantam, a positive regulator of growth. Works from various laboratories have shown that down regulation of Homothorax reduced epithelial cell growth in eye discs. Here, we tried to characterize the effects of Homothorax knockdown in glial cells and its effects on CNS growth and development at various stages of Drosophila development. Previous work from our laboratory showed that glia specific knock down of Homothorax does not reduce the glial cell number. However, in the present work, we notice that the mutant larvae displayed wedge shaped CNS phenotype with extended optic lobes. Further, we also studied the effect of Hth RNAi in embryos. In addition to that, we also noticed that Hth RNAi mutant pupae never enclosed into adults. Further, both to confirm the specificity of RNAi and rule out the off target effects of RNAi, we performed rescue experiments using mammalian homologue of Homothorax i.e. UAS Myc Meis. Glia specific expression of UAS Myc Meis completely rescued the Hth RNAi phenotype to normal. This experiment allowed us to study the functional conservation of Homothorax. Further it would be very interesting to study and characterize these phenotypes at both cellular and molecular level.

Reference :