| dc.description.abstracteng | The cell cycle mode is variant among different cell and tissue types and is remodeled during development. This change between modes is referred as cell cycle switch or remodeling. In Drosophila melanogaster, the canonical cell cycle contains G1, S, G2 and M phases. During early embryogenesis, the cell cycle mode changes from fast syncytial cycle with only S-M phases to an embryonic mode with introduction of a G2 phase. This mode switch is a prominent feature of the mid-blastula transition (MBT). However, it is unclear how the cell cycle remodeling is linked to the developmental program.
In the first part “Isolation of new germline clone mutations with blastoderm defects”, I conducted an EMS-induced mutagenesis screen to identify novel genes, which are maternally required for Drosophila blastoderm formation. 26 candidate mutants with defects in preblastoderm, blastoderm, cellularization, gastrulation as well as cell cycle were successfully isolated on the third chromosome. By means of mapping and sequencing, novel genes and new function of known genes involved in blastoderm formation have been identified.
In the second part “Role of Protein phosphatase V in Cell Cycle Control in Drosophila Blastoderm”, I characterized a novel mutation in Protein phosphatase V (PpV), the homologue of human Protein phosphatase 6 (PP6), from a genetic screen and analyzed its cell cycle function during the MBT. A G2 phase is introduced by the Tribbles and other zygotic factors induced degradation of phosphatase Cdc25/Twine in interphase 14, but the mechanisms how Cdc25/Twine protein levels are controlled and how the striking robustness of the cell cycle switch are ensured are not fully understood. I show that maternal PpV is critical in timing the cell cycle remodeling by maintaining the low Cdc25/Twine level in pre-MBT. Complementary to PpV, zygotic Tribbles is involved in the induced degradation of Cdc25/Twine during MBT by enhancing the decay rate. PpV may directly act on Cdc25/Twine, as we identified three additional phosphorylation sites of Twine in PpV mutants. Mutation of these PpV-dependent phosphorylation sites led to high proportion of extra embryonic nuclear cycle, similar to PpV mutants. | de |