Abstract
The establishment of mouse embryonic stem (ES) cells provided an excellent model to study embryonic lineages in culture and in vivo. The pluripotent cells can contribute to all embryonic tissues, including the germ line, in chimeras. Furthermore, tissues from all three germ layers have been successfully formed from ES cells in culture. These abilities have made ES cells an attractive culture system for studying the regulators of lineage-specific determination and differentiation. However, the inability of ES cells to differentiate into cells of the trophoblast lineage has precluded them from being a cell culture model for this essential extraembryonic lineage. The fibroblast growth factor (FGF4) produced by the inner cell mass (ICM) is necessary for the proliferative maintenance of the polar trophectoderm (TE), and the lack of FGF signaling in the mural region results in giant cell differentiation. FGF signaling is important for trophoblast development and could prevent giant cell transformation. Gene expression studies, TS cell line derivation potential, and mitogen activated protein kinase (MAPK) activities in the embryo have led to a precise prediction of when and where trophoblast multipotent progenitors exist in vivo. The extraembryonic visceral endoderm (VE) and parietal endoderm (PE) layers exhibit substantial growth during development, but a defined progenitor or stem cell population is yet to be identified in this cell lineage.
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