Research Summary

Elucidating the mechanisms underlying the Merlin-Hippo signaling in glia growth control in Drosophila

Glial cells are the most abundant cell type in the Central Nervous System (CNS), which play key role in the proper development and functioning of CNS. Despite their fundamental importance, mechanisms underlying the glia development and growth control are not well understood. Hippo signaling is a relatively novel tumor suppressor pathway that plays crucial role in organ growth control and homeostasis in diverse species - from flies to humans. Recently we have identified a role for Merlin - a tumor suppressor- signaling in glia development in Drosophila, and that its effects on growth can be accounted for by modulation of Hippo activity. However, the nature of upstream regulators that confer Merlin growth inhibitory functions remain obscure. Using Drosophila as a model organism; employing genetic, molecular and biochemical approaches, my study investigates Merlin-Hippo signaling function and regulation during glia development and growth. Merlin mutation has been associated with Neurofibromatosis type-2, a familial cancer syndrome with tumors of the peripheral nervous system. By achieving a better understanding of Merlin-Hippo signaling in glia development and biology, we hope to gain insights into glioma growth, permitting the development of more effective targeted therapies.

Figure Legend: Schematic model of the Merlin-Hippo signaling in Drosophila glial cells. Yorkie is the key downstream effector of the pathway and is a transcriptional co-activator. Yorkie target genes include cell cycle and apoptosis regulators. Upstream regulators in the pathway influence Yki activity by affecting its phosphorylation and localization. Pointed arrows show activating effects, block arrows show inhibiting effects.