Intercellular Affairs: Investigating Oocyte Selection and Enrichment in the Mammalian Germline Cyst

Abstract

A highly conserved feature of gametogenesis across animals is the formation of germline cysts, clusters of connected cells that arise from incomplete cytokinesis. In the Drosophila ovary, cysts form in a highly stereotyped pattern, where some cells in the cyst, designated as nurse cells, enrich a single oocyte per cyst. In contrast, mammalian cysts exhibit variability in size and connectivity, and the functional significance of cysts in mammalian gametogenesis remains unclear. In female mammals, germline cysts form during embryogenesis and females are born with the complete set of oocytes available throughout their reproductive lifespan, known as the ovarian reserve. In mice, it has been proposed that cytoplasmic and organelle transfer between germ cells enriches developing oocytes, analogous to the nursing mechanism observed in Drosophila. However, emerging evidence challenges this model, raising the possibility that oocyte growth may instead rely on cell-autonomous biosynthesis. Using a photoconvertible mitochondrial label, I investigate mitochondrial dynamics in germ cells and provide evidence that oocyte growth may be driven partly by cell-autonomous biosynthesis rather than intercellular transport. In addition to enrichment, the mechanisms underlying oocyte specification within mammalian cysts remain poorly understood. While expression of oocyte transcription factors, including Lhx8 and Nobox, are thought to be restricted to future oocytes, it is unclear whether all cells that activate these genes ultimately survive to become oocytes, or whether these factors might be shared among cells in a cyst. To investigate the spatiotemporal dynamics of Lhx8 and Nobox, I develop reporter constructs for live imaging of these factors. Together, this work provides insight into the mechanisms governing oocyte growth and selection in the mammalian germline cyst. Understanding how oocytes emerge from germline cysts has broad implications for reproductive biology, infertility, and the maintenance of the ovarian reserve.