Diffusible fraction of niche BMP ligand safeguards stem-cell differentiation

Abstract

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) 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 and find that diffusible fraction of Dpp is required to ensure differentiation of GSC daughter cells, opposite of its role in maintenance of GSC in the niche. Our work provides an example in which a soluble niche ligand induces opposed cellular responses in stem cells and in differentiating descendants so that the niche can tightly restrict its space. This may be a common mechanism to regulate tissue homeostasis. One sentence summaryBMP ligand diffuses from the niche and has dual, and opposite roles on stem cells and differentiating daughter cells.