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Vol. 16, No. 20, pp. 2650-2661, October 15, 2002
Department of Cell and Developmental Biology, University of
Pennsylvania School of Medicine,
Philadelphia, Pennsylvania 19104-6058, USA
Critical to our understanding of the developmental potential of stem
cells and subsequent control of their differentiation in vitro and in
vivo is a thorough understanding of the genes that control stem cell
fate. Here, we report that Foxd3, a member of the forkhead
family of transcriptional regulators, is required for maintenance of
embryonic cells of the early mouse embryo. Foxd3
/ embryos
die after implantation at approximately 6.5 days postcoitum with a loss
of epiblast cells, expansion of proximal extraembryonic tissues, and a
distal, mislocalized anterior organizing center. Moreover, it has not
been possible to establish Foxd3/ ES cell lines or to
generate Foxd3/ teratocarcinomas. Chimera analysis reveals
that Foxd3 function is required in the epiblast and that
Foxd3/ embryos can be rescued by a small number of wild-type cells. Foxd3/ mutant blastocysts appear
morphologically normal and express Oct4, Sox2, and
Fgf4, but when placed in vitro the inner cell mass initially
proliferates and then fails to expand even when Fgf4 is added. These
results establish Foxd3 as a factor required for the
maintenance of progenitor cells in the mammalian embryo.
[Key Words: mouse embryogenesis; stem cells; Foxd3; winged helix gene]
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