Broad, an Active Participant in Drosophila Oogenesis with Broad Functions

The follicular epithelium (FE) of the Drosophila egg chamber is an excellent model system to study cell-cycle regulation, cell differentiation and cell migration in development. During oogenesis, follicle cells sequentially undergo three distinct cell-cycle programs: the mitotic cycle (stage 1-6), endocycle (stage 7-10a), and gene amplification (stage 10b-13). Notch signaling plays a central role in regulating follicle-cell differentiation and cell-cycle switches; its activation and inactivation in follicle cells are essential for the mitotic cycle/endocycle (M/E) and the endocycle/gene amplification (E/A) switches, respectively. In my dissertation, I mainly focus on Notch signaling and its downstream target broad (br). In the first part of the dissertation, I introduce the background information of the egg chamber system, Notch signaling and other associated factors. In the second part, I describe a screen strategy to identify novel genes involved in Notch-mediated follicle cell differentiation and cell cycle switches. In the third part, I select a Notch target gene br from the above-mentioned screen and study its regulation and functions. I will show br, encoding a small group of zinc-finger transcription factors resulting from alternative splicing, is a transcriptional target of Notch nuclear effector Suppressor of Hairless (Su(H)). The early pattern of Br in the FE, uniformly expressed except in the polar cells, is established by Notch signaling around stage 6, through the binding of Su(H) to the br early enhancer (brE) region. My findings also suggest an important role of br in the timing of follicle cell development during the M/E switch. In the fourth part, I report the uniform pattern of Br in the follicular epithelium is gradually lost in the anterior follicle cells (stretched cells and border cells) from stage 9 to 10a during oogenesis. This downregulation of Br is functionally significant for proper stretched-cell stretching. I also find ecdysone and JAK/STAT signaling mediate the downregulation of Notch-maintained Br. Together, My research investigates the complex Notch signaling network, and reveal that Notch-directly-regulated Br interacts with the ecdysone and JAK/STAT pathways, serving as an important spatiotemporal cue for proper cell differentiation and morphogenetic movement during Drosophila oogenesis.