Let’s Set the Record STRA8: Germline Cysts Coordinate Meiotic Entry in Mammals

Abstract

In mice, germ cells develop in an interconnected cyst structure, but the purpose of the germline cyst is not well understood. Both males and females maintain the germline cyst structure during meiosis, the cell cycle that produces unique haploid gametes and allows for the passage of genetic information from parent to offspring. When the cyst structure is destabilized, males exhibit meiotic defects in germ cells and are infertile, and females display desynchronized meiotic entry and are subfertile. This raises the question, is one of the functions of cysts in mice to coordinate meiotic entry and progression? My thesis investigated whether cysts enable the sharing of meiotic factors by labeling STRA8 and MEIOC with the photoconvertible protein Dendra2, allowing for the selective photoconversion of single germ cells within a cyst. Stra8 is a master regulator of meiotic entry and progression, coordinating the temporally regulated G1 to S transition and serving as a transcriptional activator of meiotic genes. MeioC, a downstream target of STRA8, serves to regulate the mitosis to meiosis transition by destabilizing meiotic transcriptional repressors and mitotic cyclins, and extends prophase I by stabilizing meiotic transcripts. Live imaging of germline cysts in their native environment confirmed temporal and spatial expression of STRA8-Dendra2. Moreover, I demonstrated for the first time that STRA8 is shared across cells within a cyst, though cytoplasmic STRA8 levels were significantly more variable than a homogeneously distributed cytoplasmic protein. Together, I propose a model in which the germline cyst shares STRA8 across germ cells in a cyst, potentially serving to buffer heterogeneity of nuclear shuttling or Stra8 transcription.