Direct regulation of broad expression by Notch signaling during the mitotic/endocycle switch in Drosophila follicle cells. Dongyu Jia¹, Yoichiro Tamori¹, George Pyrowolakis^2,3, Wu-Min Deng¹. 1) Department of Biological Science, Florida State University, Tallahassee, FL 32306. USA; 2) Institute for Biology I, Faculty of Biology, Albert-Ludwigs-University of Freiburg, Hauptstrasse 1, 79104 Freiburg, Germany; 3) BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University of Freiburg, 79104 Freiburg, Germany.

   During Drosophila oogenesis, the follicle cells sequentially undergo three distinct cell-cycle programs: the mitotic cycle (stages1-6), the endoreplication cycle (also called the endocycle, stages 7-10a), and gene amplification (stages10b-13), through which chorion genes are selectively amplified. Activation of Notch signaling in the follicular epithelium (FE) at around stages 6/7 is essential for the proper entry of the endocycle. Notch induces the expression of zinc finger protein Hindsight and suppresses homeodomain protein Cut to control the mitotic/endocycle (M/E) switch. Here we report that broad (br), encoding a family of zinc-finger transcription factors, is a direct transcriptional target of Notch/Supressor of Hairless (Su(H) site binding of CSL complex (CBF-1, Su(H), Lag-1)) in the FE. We show that the early pattern of Br expression in follicle cells, uniformly expressed in the FE starting at stage 6, is established by Notch signaling. We identified a putative Su(H) binding site at the br early enhancer (brE) region, mutation of this site significantly reduced the expression of a reporter in the FE after Notch activation. The regulation of brE by Notch singlaing appears to be tissue-specific, as similar regulation does not exist at the dorsal/ventral boundary in the wing imaginal disc, where Notch is also active. We further demonstrate that br function is involved in the M/E switch and Br acts in parallel to Hnt during the endocycle.