Follicular Patterning Directed by Janus Kinase Signaling

A small number of defined signaling pathways have emerged as reutilized intracellular signaling cascades that initiate cellular responses. One of these is the Janus kinase (JAK) signaling pathway. JAK signaling is the primary component of the response of many vertebrate cells to a many cytokines and growth factors. Consequently, the JAK pathway is essential for a many developmental events, including hematopoiesis, immune system development, and general growth. The pathway has been evolutionarily conserved from insects to human. Study of JAK signaling in the fruitfly, Drosophila melanogaster, is particularly attractive because it is amenable to genetic and developmental manipulation and is much simpler than the vertebrate counterpart, with only single representatives of each type of pathway molecule. As in vertebrates, the pathway is critical to many developmental events. Previously funded NSF activities have uncovered a requirement for JAK signaling in the patterning of the follicular epithelium, the monolayer of somatic cells that covers the developing egg and forms the eggshell and specialized structures. The follicular epithelium is comprised of 5 different cell fates that are determined by their position along the anterior-posterior axis The JAK ligand, Upd, as well as a homologous protein, are secreted from the poles of the egg chamber and a gradient of JAK pathway activity is created that is highest at the anterior and posterior termini. The gradient of JAK pathway activity determines the fates of the follicular cells. This suggests that Upd may act as a classical morphogen, a molecule that patterns a field of tissue into different cell fates that are assigned by virtue of position relative to the morphogen source. The two primary goals of this research will address the hypothesis that Upd may act as a morphogen. First, the mechanisms by which a gradient of JAK pathway activity is established in the follicular epithelium will be determined. The distribution of the Upd and homologous proteins their contributions to activation of the JAK pathway and establishment of epithelial pattern will be assessed. Second, the mechanisms by which the Upd ligand is transported to receiving cells will be examined. Known morphogens are distributed by passive diffusion, active endocytic transport, or a combination of the two. The contributions of these mechanisms to distribution of Upd and homologues will be examined. The proposed research will be carried out primarily as the major training activity of graduate students. Additional roles will be played by undergraduates seeking learn about biology through conducting independent research projects. As in the past, the majority of students involved in these research activities are likely to be women and/or Kentucky natives. Results of the proposed activities will be presented at professional meetings by the students who carry out the research.