Diffusing fraction of niche BMP ligand safeguards stem-cell differentiation

Drosophila male germline stem cells (GSCs) reside at the tip of the testis and surround a cluster of niche cells. It has been believed that the niche-derived Decapentaplegic (Dpp) ligand has a role in maintaining stem cells in close proximity but has no role in the differentiating cells spaced one-cell layer away. However, the range of Dpp diffusion has never been tested. Here, using genetically encoded nanobodies called Morphotrap, we physically block Dpp diffusion without interfering with niche-stem cell signaling. When Dpp diffusion is perturbed, differentiating germ cells frequently de-differentiated, suggesting that Dpp ensures differentiation of GSC daughter cells, opposing to its role in maintenance of GSC in the niche. Our work provides the evidence that a single niche ligand induces distinct cellular responses inside versus outside the niche, which may be a common mechanism to regulate tissue homeostasis.