Developmental Control of Aeiosis and the Onset of Embryogenesis

Oogenesis accomplishes two developmental goals: halving the chromosome number by meiosis and differentiation of the oocyte. The differentiated oocyte is stockpiled with maternal components required to direct embryogenesis until expression of the zygotic genome. In most animals meiosis arrests first in prophase I to permit oocyte differentiation; a secondary arrest point coordinates completion of meiosis with fertilization. Release of both of these arrest points is accompanied by translation of stored maternal mRNAs, and we are taking genomic approaches to identify these translated mRNAs. We recovered mutants in which the meiotic arrests fail to occur or be released, and these likely define key developmental regulators of meiosis. For example, these studies identified a meiosis-specific activator of the Anaphase Promoting Complex/Cyclosome, the product of the cortex gene, and demonstrated that this form of the Anaphase Promoting Complex is uniquely required for completion of meiosis in the oocyte.

We identified the PAN GU (PNG) protein kinase complex that controls the onset of embryonic division and the transition from maternal to zygotic control by regulating translation. This kinase complex is composed of a ser/thr kinase catalytic subunit, PNG, and two activating subunits, PLU and GNU. The PNG kinase complex controls the oscillations between DNA replication and mitosis that occur in the rapid embryonic divisions by ensuring adequate levels of Cyclin B are translated. Sufficient levels of CyclinB lead to active CDK1/Cyclin B kinase (or MPF) that acts to block re-initiation and DNA replication and to initiate mitosis. PNG controls Cyclin B translation by poly (A)-dependent and independent mechanisms. Later in embryogenesis, PNG promotes the translation of the SMAUG protein, which recruits the deadenylase complex to maternal mRNAs, leading to their degradation.