CELL BIOLOGY: Safe in the Womb

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Science  13 Jun 2003:
Vol. 300, Issue 5626, pp. 1623b
DOI: 10.1126/science.300.5626.1623b

Mammalian embryos are surrounded by the trophoblast giant cell layer, an epithelial layer that forms a barrier between maternal and embryonic tissues. Jaquemar et al. examined mutant mice deficient in an intermediate filament protein, keratin 8. The majority of mouse embryos lacking keratin 8 fail to develop beyond midgestation. However, chimeric concepti in which the embryonic tissues lacked keratin 8 but contained extraembryonic tissue derived from tetraploid wild-type cells could develop, suggesting that a failure in the trophoblast giant cell layer could be responsible for the embryonic deaths. The growth factor TNF (tumor necrosis factor) contributed to breaching epithelial integrity because, in the absence of maternal TNF, more keratin 8- deficient embryos were able to survive. When TNF-dependent apoptosis was induced by the addition of concanavalin A, mutant embryos lacking keratin 8 were more likely to fail because of the formation of hematomas at sites of trophoblast giant cell layer barrier breakage. Thus, this epithelial keratin plays an important role in protecting trophoblast giant cells from maternal TNF-induced apoptosis and enabling the embryo to develop to term.—SMH

J. Cell Biol. 161, 749 (2003).

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