2018 Theses Doctoral

Investigating The Role Of Signaling Pathways In Adult Stem Cells Governed By Population Asymmetry

Melamed, David Eric

Adult stem cells are vital to animal biology, tasked with replenishing cells in a variety of tissue types. Historically, there have been two contrasting models of stem cell behavior, “single-cell asymmetry,” where each stem cell is generally long lived and is responsible for perpetual daughter (non-stem) cell production, and “population asymmetry,” where a group of stem cells maintain population numbers while producing non-stem cell daughters, but individual stem cells undergo stochastic competition leading to frequent loss or amplification of individual lineages. Our work examines Drosophila ovarian Follicle Stem Cells (FSCs), which are somatic adult stem cells organized as a population of 14-16 cells within each germarium. FSCs are responsible for the production of two distinct somatic daughter cell types at opposite borders of the stem cell population. The FSCs are arranged in three anteroposterior layers; posterior “layer 1” FSCs divide faster and directly produce Follicle Cells (FCs), while anterior “layer 2 and 3” FSCs divide more slowly and give rise to Escort Cells (ECs). We have examined how signaling pathways contribute individually to FSC behavior, using clonal analysis to manipulate individual FSC genotypes and subsequently determine how autonomous FSC properties and competition among FSCs is affected. Our data indicate that Janus Kinase/Signal Transducers and Activators of Transcription (JAK-STAT) and Wnt pathways are primarily responsible for regulating location, proliferation and differentiation in FSCs. The activities of Hedgehog (Hh), Hippo (Hpo), and Phosphoinositide 3-kinase (PI3K) pathways are also shown to be important for FSC competition.