Salt Inducible Kinases in Drosophila Neural Development.

Salt Inducible Kinases in Drosophila Neural Development. Bahar H. Sahin¹, Sercan Sayin^1,2, Nic Tapon³, Arzu Celik¹. 1) Molekuler Biyoloji ve Genetik Bolumu, Bogazici Universitesi, Istanbul, Turkey; 2) Max Planck Institute of Neurobiology, Munchen, Germany; 3) London Research Institute, Lincolns Inn Fields Laboratories, London, UK.

Salt inducible kinases (SIKs) are Ser/Thr kinases from AMPK-RK family, and involved in insulin metabolism. Upon regulation by PKA signal, SIKs regulate CRTC activity. SIKs are target of a master tumor suppressor kinase Lkb-1; accordingly many instances of cancer progression exist. Here we model the highly conserved SIK homologs in Drosophila. Like the mammalian ortholog, Drosophila SIK2 interacts with the FGF pathway in the course of insulin metabolism; while SIK3 is poorly characterized. Recently SIK3 was shown to affect glucose/lipid homeostasis, skeletal and adipocyte development. Yet the molecular interactions SIK3 goes through remain largely unknown. We started to characterize the role of SIK2 and SIK3 in nervous system development using the Drosophila compound eyes as a model. We generated the SIK3 null mutants and used the conventional Drosophila genetic techniques to elucidate function of SIKs. SIK modulation causes tumors, showing a role in cancer as well. We have also shown that both SIK2 and SIK3 are involved in eye development, regulating eye size and cell specification events. Using scanning electron microscopy, we have seen that bristles and lenses are disrupted in mutants. To understand the defect in more detail, we analyzed late larval and early pupal expression of SIK3. Behind the morphogenetic furrow, SIK3 is expressed in the nuclei of neural cell, as well as other cells that are currently under investigation. Midpupal eyes will soon be dissected to understand SIK3 role on the specification. Meanwhile, we have seen that SIKs interact with the Notch pathway. Currently, we are trying to identify the pathway member SIKs are interacting with, and the mode of interaction by the genetic approach. Once SIK partner is identified, the role of SIKs in cell proliferation and apoptosis will be investigated as well. Thus, in this project, our aim is to attribute a defined role in neural development and cell specification to Drosophila SIK genes.