INTRODUCTION The first cell-lineage specification and restriction in mammalian development occurs in preimplantation embryos, when blastocysts form from compacted morulae. They consist of an outer cell population, the trophectoderm, from which the trophoblast compartment of the extra-embryonic tissues

The first cell-lineage specification and restriction in mammalian development occurs in preimplantation embryos, when blastocysts form from compacted morulae. They consist of an outer cell population, the trophectoderm, from which the trophoblast compartment of the extra-embryonic tissues develops and an inner cell population, the inner cell mass or embryoblast, from which all tissues of the embryo proper, the yolk sac, the amnion and the allantois, develop. The cells of the inner cell mass are, therefore, a transient pluripotent stem cell population of the embryo proper and some extraembryonic tissues (reviewed by Hogan et al., 1994). Cells are pruned from this population by programmed cell death (Smith and Wilson, 1971). This presumably occurs as a counterbalance to excessive cell proliferation or to remove cells that started to differentiate into an undesirable direction (Pierce et al., 1989). In wild-type E3.5 embryos up to 10% of inner cell mass cells have been observed to undergo apoptosis, but cell death is not observed in the trophectoderm lineage at this point (reviewed by Sanders and Wride, 1995, and by Pampfer and Donnay, 1999). Electron microscopy, vital dye exclusion and in situ end-labelling studies have shown that the cells dying in the inner cell masses exhibit the typical signs of apoptosis (Copp, 1978; Handyside and Hunter, 1986; Brison and Schultz, 1997). 5449 Development 127, 5449-5461 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 DEV2556