Alternative splicing (AS) allows distinct proteins to be encoded by a single gene. Although AS is necessary for development and homeostasis, its role in the germline is unclear. Now, Xin Wu and colleagues investigate the role of epithelial splicing regulatory protein 1 (ESRP1), which functions in epithelial cell-specific splicing, during mouse oogenesis. The authors generate a germline-specific knockout of Espr1 and observe that, although male mice are unaffected, female mice are infertile. Morphological analyses reveal that Espr1-knockout ovaries are smaller, with significantly fewer follicles and impaired ovulation. The researchers use immunofluorescence and chromosome spread assays to identify defects in spindle and chromosome organisation in the maturing oocytes, which cause meiotic arrest at metaphase I. Furthermore, they show that kinetochore-microtubule attachments are reduced or mismatched in ESPR1-deficient animals. Single cell RNA-seq reveals that oocyte meiosis-related genes are downregulated in Esrp1-knockout ovulated oocytes. Finally, by analysing splicing dynamics, the authors show that a long-protein isoform of LSM14B (which binds to tubulin and is essential for spindle stability) increases in abundance in ESPR1-deficient oocytes. Together, these results indicate that ESRP1-mediated AS might be required for maintaining spindle morphogenesis and oocyte meiosis during mammalian germline development.
