DNA replication and compaction in the cleaving embryo of the mouse.
The effects of aphidicolin, a reversible inhibitor of DNA polymerase alpha, both on replication and on development of the mouse embryo from the 2- and 4-cell stages to the compacted late 8-cell stage have been assessed. The continuous presence of aphidicolin from G1 of the 4-cell stage resulted in inhibition of DNA replication and prevention of division from 4 to 8 cells, but was without effect on the timing or incidence of cell flattening, surface polarization and cytoplasmic polarization. The continuous presence of aphidicolin from G1 of the 2-cell stage resulted in inhibition of DNA replication, division, and polarization. Some slight intercellular flattening in a few embryos did occur. If addition of aphidicolin was delayed by 10 h to early in G2 of the 2-cell stage, further rounds of replication were blocked and some embryos failed to cleave to 4-cells. Nevertheless, almost all embryos showed evidence of flattening and polarization regardless of cell number. In contrast, if aphidicolin was added in G1 of the 2-cell stage and removed after 10 h, the cells showed delayed DNA replication, little evidence of division, and no cell flattening or polarization. We conclude that DNA replication at the 2-cell stage may be essential for the components of compaction studied, but that DNA replication at the 4- and 8-cell stages is not.
D000818:Animals; D016590:Aphidicolin; D001757:Blastomeres / Q000032:analysis; D002453:Cell Cycle; D002970:Cleavage Stage, Ovum / Q000166:cytology / Q000187:drug effects*; D004247:DNA / Q000032:analysis; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors; D004261:DNA Replication / Q000187:drug effects*; D004224:Diterpenes / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000648:ultrastructure; D005314:Embryonic and Fetal Development; D005260:Female; D051379:Mice; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence
D004224:Diterpenes; D016590:Aphidicolin; D004247:DNA; D004257:DNA Polymerase II