Apoptosis in mouse embryos: elevated levels in pregastrulae and in the distal anterior region of gastrulae of normal and mutant mice.

The pattern of apoptotic cell death has been surveyed in prestreak and primitive streak embryos of four strains of mice and in three mutants affecting gastrulation. In C57BL/6 embryos, a high level of cell death occurs in the early egg cylinder stage at embryonic day 5 (E5) to E5.5. In all strains, cell death is elevated shortly before gastrulation, but the level varies four- to fivefold among strains. During gastrulation, cell death declines but is relatively more abundant in the distal and distal anterior regions. Early streak embryos cultured in media with reduced levels of growth factors show increased cell death mainly in the distal region. In three mutants with disturbed function of the proximal visceral endoderm and/or primitive streak, cell death is increased, and the regional pattern seen in normal embryos is intensified. The results strongly suggest that the proximal visceral endoderm and primitive streak region are the principal sites of synthesis of growth factors promoting cell survival. We conclude that localized growth factor supply has an important role in regulating the size of the embryo and of embryonic regions.