Adhesion-controlled mechanics of the glial niche regulate neural stem cell proliferative potential

Stem cell proliferation drives tissue formation and homeostasis. Whether and how niche cell mechanics act in vivo to control this process remains unclear. Here, we identify a triad of cell adhesion molecules from the immunoglobulin superfamily, which physically link neural stem cells (NSCs) to their glial niche in Drosophila. Disrupting this connection increases actomyosin activation and tensile forces in the glial cells, reciprocally causing mechanical stress in NSCs. This promotes lamin accumulation, which causes nuclear deformation and acts as a protective response safeguarding NSC mitosis. However, this response is insufficient, and NSCs display abnormal spindle morphologies and impaired mitotic progression. Ultimately, the loss of NSC and niche mechanical interplay compromises NSC proliferative potential and genome integrity. This study uncovers a fundamental role for niche cell mechanics and members of the immunoglobulin superfamily, acting as mechanoregulators, in controlling stem cell proliferation.