FOXL2 interaction with different binding partners regulates the dynamics of ovarian development

The transcription factor FOXL2 is required in ovarian somatic cells for female fertility. Differential timing of Foxl2 deletion, in embryonic versus adult mouse ovary, leads to distinctive outcomes suggesting different roles across development. Here, we comprehensively investigated FOXL2’s role through a multi-omics approach to characterise gene expression dynamics and chromatin accessibility changes, coupled with genome-wide identification of FOXL2 targets and on-chromatin interacting partners in granulosa cells across ovarian development. We found that FOXL2 regulates more targets postnatally, through interaction with factors regulating primordial follicle activation (PFA) and steroidogenesis. Deletion of one interactor, Ubiquitin specific protease 7 (USP7), induces PFA blockage, impaired ovary development and sterility. Our datasets constitute a comprehensive resource for exploration of the molecular mechanisms of ovarian development and causes of female infertility.