Notch controls APC/C FZR-1 to enable accumulation of chromatin regulators in germline stem cells from Caenorhabditis elegans
- David Puerta
- Sara Rivera-Martín
- Adrián Fragoso-Luna
- Susan Strome
- Sarah L Crittenden
- Judith Kimble
- José Pérez-Martín
2025-05-30
Originally known for its function in the cell cycle, the anaphase-promoting complex/cyclosome (APC/C) also plays a crucial role in regulating differentiation and maintaining cell identity. However, the mechanisms by which APC/C mediates developmental processes are not fully understood. In this study, we show that APC/C and its activator FZR-1 regulate the chromatin regulators MES-4 and MES-3. These proteins are part of histone methylation complexes essential for maintaining germline stem cell (GSC) identity in the germ line of Caenorhabditis elegans . APC/C FZR-1 facilitates the degradation of MES-4 and MES-3 when GSCs transition toward differentiating into oocytes. The activity of APC/C FZR-1 is restricted by the Notch signaling pathway provided by the distal tip cell, which is responsible for maintaining the stemness of the GSC pool. This negative regulation enables the accumulation of MES-3 and MES-4 in GSCs, offering an additional component by which niche activity modulates the C. elegans germ line.