Year of Publication

2002

Document Type

Dissertation

College

Arts and Sciences

Department

Biology

First Advisor

John Rawls

Abstract

The JAK-STAT pathway is an intracellular signaling pathway that is found to have crucial roles in hematopoiesis, immune response and the development of many other tissues in mammals. The pathway is conserved in Drosophila melanogaster, and is much simpler: there is only one Drosophila JAK (Hopscotch, Hop) and STAT (STAT92E) respectively, while there are at least 4 JAKs and 7 STATs in mammals. The pathway has been intensively studied in Drosophila, and has been implicated in many tissue development and cellular processes. In this work, I present several roles of JAK signaling in oogenesis.First, JAK signaling is required for cell differentiation within a specific lineage of follicle cells – stalk cells and polar cells. Unpaired (upd), which encodes the known ligand for the pathway, is expressed specifically in the polar cells in the developing egg. Reduced function of Upd or Hop results in fusions of egg chambers, which is primarily caused by improper formation of stalk cells, while general activation of the pathway in the egg chamber produces an extra number of stalk cells and sometimes eliminates polarfollicle cells. Based on the known function of the Notch pathway in oogenesis, we propose a model that Notch signaling determines a pool of precursors for the polar and stalk cells while JAK activity determines their specific fates within that pool.Second, JAK signaling is also involved in epithelial follicle cell differentiation. Consistent with the expression pattern of upd in the ovary, there is a gradient of JAK activity expanding from the poles, and this JAK activation gradient is both required and sufficient to suppress the main body follicle cell fate. Also, different levels of JAK activity are required and sufficient to determine both anterior and posterior terminal follicle cell fates. Consistent with these data is a model that a gradient of JAK activity triggered by Upd from the poles pre-patterns the epithelium into three domains and pre-determines sub-populations of terminal follicle cell fates prior to the EGFR activation, and cooperates with EGFR activity later to define posterior terminal follicle cell fates. This provides the first evidence for a morphogenic function of the JAK-STAT pathway in any organism.

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