Abstract

Abstract:

The maturation of functional eggs in ovarian follicles is a critical process during early mammalian development. However, the underlying mechanisms driving robust follicle growth remain enigmatic. Recent studies showed that follicle growth is sensitive to mechanical environment, calling for a need to understand mechanical signalling within follicles. Here, we investigate the mechanical functions of theca cells (TCs) that encapsulate the follicles. Combining bioengineered ex vivo assays with biophysical and molecular approaches, we demonstrate that the contractile TCs exert compressive stress to tune intra-follicular pressure, thereby regulating oocyte signalling and follicle growth. We further showed that TC YAP signalling, proliferation and migration are tuned by substrate stiffness and curvature. Interestingly, spontaneous TC flow regulates selective growth of follicles in a doublet, augmenting their role in follicle growth competition during ovarian development. Finally, I will present findings on the role of cell death and cell-cell interfacial tension in driving self-tuned criticality and phase separation during luminogenesis at later stage of development. By modelling the follicular interior as a binary fluid, we can recapitulate the distinct morphological features of lumen and their dynamics in various follicle stages. Collectively, our studies highlight the importance of mechanical stress and tissue hydraulics in controlling the maturation of functional eggs that are crucial for future embryogenesis.