Essential to sexual reproduction is the generation of haploid gametes from diploid germ cells through meiosis – a specialised reductive form of cell division that occurs exclusively in the gonads. In contrast to the well-studied chromosomal events which take place during meiosis, the molecular mechanism underlying the mitosis-meiosis decision is poorly understood. In the presence of germ cell competence factor Dazl, extrinsic signalling molecule retinoic acid (RA) activates Stra8 expression, which is required for meiotic DNA replication in both sexes. It is unclear, however, whether additional signalling molecules are needed and what molecular changes ensure germ cells embark on meiosis. A recent study of primordial germ cell (PGC)-like cells (PGCLCs) suggested RA alone is insufficient to induce the female germ cell fate, and that the addition of bone morphogenetic protein (BMP) enhances primary oocytes production in vitro1.
In mice, Bmp2 is expressed in the fetal ovary after sex determination, suggesting a potential role for BMP2 in germ cell development. Making use of the mouse model system, we are investigating whether BMP is needed for meiosis in vivo and, if so, how, and during which step(s) of meiosis BMP signalling might be required. Specifically, we are performing conditional knockout of BMP receptors at various stages in mice, and examining the effect of these perturbations on meiosis and fertility in the female. We are also conducting expression profiling of ovarian tissue from such embryos, comparing results with our existing ‘early meiosis’ marker data, to determine which genes are likely BMP-regulated. We believe the findings of this project will be an important step towards a thorough understanding of mitosis-to-meiosis transition in mammalian germ cells. The knowledge will answer essential questions in reproductive biology, and potentially pave the way to in vitro generation of gametes and future attempts to treat infertility.