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Abnormal S-phase regulation in Cul-3^/ embryos. Shown here are blastocysts isolated at 4-day p.c. from wild-type (left) and Cul-3^/ (right) mice, cultured in vitro for 3 days, and stained with DAPI to visualize the DNA. Both blastocysts developed an inner cell mass and migratory trophoblast giant cells. Wild-type trophoblasts underwent repeated endoreduplication cycles. In Cul-3^/ trophoblast cells, endoreduplication was inhibited, possibly due to high levels of cyclin E. (For details, see Singer et al., p. 2375).