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The JAK/STAT pathway in Drosophila h...

Shen, Ying.

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The JAK/STAT pathway in Drosophila hematopoiesis: Function and regulatory mechanisms.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	The JAK/STAT pathway in Drosophila hematopoiesis: Function and regulatory mechanisms./
作者:	Shen, Ying.
面頁冊數:	182 p.
附註:	Adviser: Soichi Tanda.
Contained By:	Dissertation Abstracts International68-12B.
標題:	Biology, Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3292883
ISBN:	9780549366058

The JAK/STAT pathway in Drosophila hematopoiesis: Function and regulatory mechanisms.
Shen, Ying.

The JAK/STAT pathway in Drosophila hematopoiesis: Function and regulatory mechanisms. - 182 p.

Adviser: Soichi Tanda.

Thesis (Ph.D.)--Ohio University, 2007.

The evolutionarily conserved JAK/STAT pathway plays a critical role in Drosophila hematopoiesis. A gain-of-function mutation of the Janus kinase (JAK), hopscotchTumorous-lethal (hop Tum-l), leads to hemocyte overproliferation and abnormal lamellocyte differentiation. In this study, I demonstrated that effects of hopTum-l were manifested in different types of hemocytes and its activity was regulated in various ways. Firstly, hop Tum-l affects 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 Drosophila SUMO conjugase Lesswright (Lwr) and the putative Drosophila SUMO ligase protein inhibitor of activated STAT (dPIAS) in the JAK/STAT pathway, lwr and dpias were expressed in the hopTum-l background. Expression of lwr and dpias both suppressed hopTum-l-induced hemocyte overproduction and the effects were additive, which raises the possibility that lwr and dpias negatively 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 hopTum-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 hopTum-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 Drosophila larval hematopoiesis.

ISBN: 9780549366058Subjects--Topical Terms:

1017730
Biology, Genetics.

The JAK/STAT pathway in Drosophila hematopoiesis: Function and regulatory mechanisms.
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520 $a The evolutionarily conserved JAK/STAT pathway plays a critical role in Drosophila hematopoiesis. A gain-of-function mutation of the Janus kinase (JAK), hopscotchTumorous-lethal (hop Tum-l), leads to hemocyte overproliferation and abnormal lamellocyte differentiation. In this study, I demonstrated that effects of hopTum-l were manifested in different types of hemocytes and its activity was regulated in various ways. Firstly, hop Tum-l affects 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 Drosophila SUMO conjugase Lesswright (Lwr) and the putative Drosophila SUMO ligase protein inhibitor of activated STAT (dPIAS) in the JAK/STAT pathway, lwr and dpias were expressed in the hopTum-l background. Expression of lwr and dpias both suppressed hopTum-l-induced hemocyte overproduction and the effects were additive, which raises the possibility that lwr and dpias negatively 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 hopTum-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 hopTum-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 Drosophila larval hematopoiesis.
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