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First published online November 17, 2003
doi: 10.1242/10.1242/dev.00893

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Mouse embryonic chimeras: tools for studying mammalian development

¹ Embryology Unit, Children's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia
² Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

View larger version (38K): [in a new window]   Fig. 1. Mouse embryos at the periimplantation (A, day 4.5) and post-implantation (B, day 6.0; C, day 7.0) stages of development, showing the allocation of derivatives of the inner cell mass/epiblast, primitive endoderm and trophectoderm, to different tissue compartments of the conceptus. The inner cell mass is the precursor of the epiblast of day 6.0 embryos, and the transition between these two tissues is likely to be a progressive process (Rathjen et al., 2002). The epiblast gives rise to ectoderm, mesoderm and definitive endoderm. The primitive endoderm of the day 4.5 embryo is derived from the inner cell mass. It differentiates into parietal and visceral endoderm (both contribute to fetal extra-embryonic membranes). The trophectoderm gives rise to the ectoplacental cone, extra-embryonic ectoderm and the trophoblast giant cells. The Reichert's membrane is a composite layer of trophoblast giant cells, the basement membrane and the parietal endoderm.

View larger version (59K): [in a new window]   Fig. 2. Lineage contributions of different types of cells used in the construction of four types of embryonic chimeras: (A) embryoembryo chimera; (B) ES (embryonic stem) cellsembryo chimera; (C) ES cells4N (tetraploid) embryo chimera; and (D) TS (trophectodermal stem) cellsembryo chimera. (I) The production of chimeras. (IA) embryoembryo chimera produced by the aggregation of two eight-cell embryos. (IB) ES cellsembryo chimera produced by the aggregation of ES cells with an eight-cell embryo (top) or by injecting ES cells into the blastocyst (bottom). (IC) ES cells4N (tetraploid) embryo chimera produced by the aggregation of ES cells with two tetraploid four-cell embryos (top) or by injecting ES cells into a tetraploid blastocyst (bottom). (ID) TS cellembryo chimera produced by injecting TS cells into a blastocyst. Introduced cells are dark green in order to represent green fluorescent protein (GFP) expression and the host cells are pale yellow. Cells of tetraploid embryos are dark yellow. (II) The different patterns of contribution by the GFP-expressing cells to different tissue compartments in the four types of chimeras developed to the early postimplantation stage (days 5.5 to 6.5) after transfer to pseudopregnant female mice for implantation and further development. (IIA) Day 6.5 embryo: GFP-expressing cells from the eight-cell embryos are found in the visceral endoderm (ve), which covers the extra-embryonic ectoderm and the epiblast. The epiblast also contains GFP-expressing cells. The broken line traces the primitive endoderm layer of the embryo. (IIB) Day 6.5 embryo: GFP-expressing ES-derived cells are found only in the epiblast (ep). (IIC) Day 5.5 embryo: exclusive contribution of GFP-expressing cells to the epiblast (ep). (IID) Day 5.5 embryo: exclusive contribution of GFP-expressing cells to the trophectoderm derivatives: extra-embryonic ectoderm (ex), Reichert's membrane (rm). The broken line marks the epiblast, which is not populated by GFP-expressing cells. (III) Day 6.0 pre-streak stage embryo illustrating the pattern of distribution of the GFP-expressing cells (shown in II) in the epiblast (ep), primitive endoderm (pe) and trophectoderm (te) derivatives. (IV) The different pattern of chimerism in the fetus proper, extra-embryonic membranes (rm, Reichert's membrane; vys, visceral yolk sac) and the placenta (pl) of the mouse conceptus at early organogenesis stage (day 9.5). For clarity, chimerism of the derivatives of extra-embryonic mesoderm, which is concordant with that of the fetus proper, is not shown.