Brinker regulates reciprocal outcomes of BMP signal between stem cells and differentiating cells

Drosophila male germline stem cells (GSCs) reside at the testis tip, surrounding a cluster of niche cells known as the hub. Bone Morphogenetic Protein (BMP) ligands secreted from the hub exert both contact-dependent and -independent effects. In close proximity to the niche, BMP signaling maintains stem cells by suppressing transcription of the key differentiation factor Bag of Marbles (Bam). In contrast, the diffusible fraction of BMP promotes differentiation of cells by activating bam expression. How a single signaling pathway produces such opposing outcomes has remained unclear. Here, we show that the diffusible BMP fraction induces bam transcription by repressing the transcriptional repressor Brinker (Brk). We further found that brk mRNA and protein display a highly heterogeneous distribution pattern within interconnected spermatogonia, suggesting that Brk has a distinct role in a subset of transit-amplifying cells. Taken together, our findings suggest a mechanism whereby a single niche-derived factor modulates reciprocal outcomes inside versus outside the niche, which is essential for tissue homeostasis. Given the widespread role of BMP signaling across stem cell niches, this mechanism might represent a general strategy for balancing stem cell self-renewal and differentiation.