Epiblast fragmentation by shedding-a novel mechanism to eliminate cells in post-implantation mouse embryos.

The role of programmed cell death during embryonic development has been described previously, but its specific contribution to peri- and post-implantation stages is still debatable. Here, we used transmission electron microscopy and immunostaining of E5.5-7.5 mouse embryos to investigate death processes during these stages of development. We report that in addition to canonical apoptosis observed in E5.5-E7.5 embryos, a novel type of cell elimination occurs in E7.5 embryos among the epiblasts at the apical side, in which cells shed membrane-enclosed fragments of cytosol and organelles into the lumen, leaving behind small, enucleated cell remnants at the apical surface. This process is caspase-independent as it occurred in Apaf1 knockout embryos. We suggest that this novel mechanism controls epiblast cell numbers. Altogether, this work documents the activation of two distinct programs driving irreversible terminal states of epiblast cells in the post-implantation mouse embryo.