The JAK/STAT pathway in Drosophilahematopoiesis: function and regulatory mechanisms
The evolutionarily conserved JAK/STAT pathway plays a critical role in Drosophilahematopoiesis. A gain-of-function mutation of the Janus kinase (JAK), hopscotch Tumorous-lethal( hop Tum-l), leads to hemocyte overproliferation and abnormal lamellocyte differentiation. In this study, I demonstrated that effects of hop Tum-lwere manifested in different types of hemocytes and its activity was regulated in various ways. Firstly, hop Tum-laffects proliferation and differentiation of hemocytes in a temperature-dependent manner. Male larvae raised at a lower temperature exhibited the most pronounced effect in hemocyte proliferation and were used for further study. Activation of the JAK/STAT pathway in specific compartments of the lymph gland resulted in different proportions of terminally differentiated hemocytes. Furthermore, to understand the regulatory roles of the DrosophilaSUMO conjugase Lesswright (Lwr) and the putative DrosophilaSUMO ligase protein inhibitor of activated STAT (dPIAS) in the JAK/STAT pathway, lwrand dpiaswere expressed in the hop Tum-lbackground. Expression of lwrand dpiasboth suppressed hop Tum-l-induced hemocyte overproduction and the effects were additive, which raises the possibility that lwrand dpiasnegatively regulate the JAK/STAT pathway through SUMOylation. Finally, the JAK/STAT pathway interacts with the Toll (Tl) pathway, another important pathway involved in larval hematopoiesis. Removal of the Tl pathway transcription factors, Dl and Dif, did not diminish hop Tum-l-induced hemocyte overproduction. Moreover, activation of the Tl pathway led to nuclear accumulation of activated Stat mainly in lamellocytes, which suggests that the Tl pathway may be functionally upstream of the JAK/STAT pathway in lamellocyte differentiation. On the other hand, activation of the Tl pathway suppressed hop Tum-l-induced hemocyte overproduction, possibly through downstream component Dl. This suppression was observed primarily in plasmatocytes, the professional phagocytes of Drosophila. This study revealed specific requirements of the JAK/STAT pathway and its interactions with the Tl pathway in a hemocyte type-specific manner. It has also demonstrated a functional relationship between the JAK/STAT and the Tl pathways in Drosophilalarval hematopoiesis.
School Location:USA - Ohio
Source Type:Master's Thesis
Keywords:drosophila hematopoiesis jak stat pathway sumoylation toll
Date of Publication:01/01/2007