The Bric-à-Brac transcription factors are necessary for formation of functional germline stem cell niches through control ofdppexpression in theDrosophila melanogasterovary

AbstractMany studies have focused on the mechanisms of stem cell maintenanceviatheir interaction with a particular niche or microenvironment in adult tissues, but how formation of a functional niche is initiated, including how stem cells within a niche are established, is less well understood. AdultDrosophila melanogasterovary Germline Stem Cell (GSC) niches are comprised of somatic cells forming a stack called a Terminal Filament (TF) and underlying Cap Cells (CCs) and Escort Cells (ECs), which are in direct contact with GSCs. In the adult, the Engrailed (En) transcription factor is specifically expressed in niche cells where it directly controls expression of thedecapentaplegicgene (dpp) encoding a member of the Bone Morphogenetic Protein (BMP) family of secreted signaling molecules, which are key factors for GSC maintenance. In late third instar larval ovaries, in response to BMP signaling from newly-formed niches, adjacent primordial germ cells become GSCs. Thebric-à-bracparalogs (bab1andbab2) encode BTB/POZ-domain containing transcription factors, that are also expressed in developing GSCs niches where they are required for TF formation. Here, we demonstrate that Bab1 and Bab2 display redundant cell autonomous function for TF morphogenesis and we identify a new function for these genes in GSC establishment. Moreover, we show that Bab proteins controldppexpression in otherwise correctly specified CCs, independently of En and its paralog Invected (Inv). In fact, our results also indicate thaten/invfunction in larval stages are neither essential for TF formation, nor GSC establishment. Finally, whenbab2was overexpressed in ovarian somatic cells outside of the niche, whereen/invwere not expressed, ectopic BMP signaling activation was induced in adjacent germ cells of adult ovaries, which formed GSC-like tumors. Together, these results indicate that Bab transcription factors are positive regulators of BMP signaling for acquisition of GSC status.