Date of Award
Doctor of Philosophy (PhD)
Cell & Molecular Biology
Adult stem cells have the unique ability to either self-renew or differentiate, thus giving them tremendous therapeutic potential. These tissue-specific stem cells are directed to self-renew by signals from the local microenvironment termed the stem cell niche. While reconstitution assays have demonstrated the existence of stem cell niches in many adult organs, unambiguous identification of the resident stem cells and their niche cells continues to be a challenge. Accordingly, the mechanisms that direct specification and formation of a stem cell niche in vivo remain unclear. The Drosophila testis has emerged as a powerful system in which to study stem cell-niche interactions. The niche cells, called hub cells, form a small aggregate at the apical tip of the testis. Hub cells promote attachment and self-renewal in the germline stem cells and cyst stem cells, which are organized in a radial array around the hub. The signaling pathways that direct the maintenance and differentiation of these lineages have been well characterized; however, the initial specification and organization of the niche is still being elucidated. It was previously shown that Notch activation in a subset of somatic gonadal precursors specifies them as hub cells in the embryonic gonad. Here we use genetic analysis to show that Notch signaling activates a branched pathway for hub cell differentiation. Along one arm of the pathway, the Maf factor Traffic jam is downregulated to allow for niche signaling and adhesion. Along a separate arm, the transcription factor Bowl, promotes the assembly of hub cells at the anterior of the gonad where they recruit and organize stem cells. We also use live imaging to reveal two phases of niche morphogenesis; 1) a sorting and guidance phase in which hub cells are directed to the anterior by an extra-gonadal cue and 2) a compaction phase characterized by the formation of an acto-myosin cable around the compacting hub concomitant with the onset of oriented GSC divisions. These observations suggest a model in which the germ cells shape their own niche by driving hub compaction. These findings greatly advance our understanding of how a stem cell niche develops within a tissue.
Wingert, Lindsey, "Specification and Morphogenesis of the Drosophila Testis Niche" (2015). Publicly Accessible Penn Dissertations. 2097.