Affiliations: 1) Icahn School of Medicine at Mount Sinai; 2) University at Albany, SUNY
Keywords: b. oogenesis; b. germline stem cell
The continuity of sexually reproducing organisms depends on germ cells. Differentiating germ cells undergo meiosis to give rise to oocytes in females, which upon fertilization launches the next generation. Once the oocyte fate is specified, oocytes synthesize mRNAs and proteins, called the maternal contribution, that regulate development of the early embryo. My lab utilizes the Drosophila female germline to ask the following questions: How is germ cell entry into meiosis controlled? And what mechanisms eliminate the mitotic germ cell-specific programs upon acquisition of oocyte fate? My lab has discovered that production of viable oocytes depends on a stepwise progression through previously unidentified programmatic steps. First, that coordination of female germ cell differentiation and meiotic entry is governed by the male-specific lethal (Msl) complex member, Msl3, which licenses the expression of genes required for these programs. Further, we found that once germ cells have differentiated and committed to meiosis-I, genes critical for promoting differentiation are transcriptionally silenced by a feedback loop between heterochromatin and the Nucleopore complex. In addition, a cohort of perduring RNAs that promote germ cell differentiation and meiosis-I are removed by the No-Go Decay RNA surveillance pathway members. Finally, loss of transcriptional silencing or failure to remove perduring RNAs that promote differentiation and meiosis-I disrupts acquisition of the maternal contribution and causes loss of the oocyte fate. I will share our recent findings on the mechanisms regulating translation of meiotic proteins and the trigger that initiates silencing of the germ cell program.