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Vol. 13, No. 14, pp. 1834-1846, July 15, 1999
1 Department of Anatomy and Program in Developmental
Biology, and 2 Department of Pediatrics, School of Medicine,
University of California at San Francisco,
San Francisco, California 94143-0452 USA
Fgf8 and Fgf4 encode FGF family members that are
coexpressed in the primitive streak of the gastrulating mouse embryo.
We have analyzed the phenotype of
Fgf8
/ embryos and discovered
that they fail to express Fgf4 in the streak. In the absence of
both FGF8 and FGF4, epiblast cells move into the streak and undergo an
epithelial-to-mesenchymal transition, but most cells then fail to move
away from the streak. As a consequence, no embryonic mesoderm- or
endoderm-derived tissues develop, although extraembryonic tissues form.
Patterning of the prospective neuroectoderm is greatly perturbed in the
mutant embryos. Anterior neuroectoderm markers are widely expressed, at
least in part because the anterior visceral endoderm, which provides
signals that regulate their expression, is not displaced proximally in
the absence of definitive endoderm. Posterior neuroectoderm markers are
not expressed, presumably because there is neither mesendoderm
underlying the prospective neuroectoderm nor a morphologically normal
node to provide the inductive signals necessary for their expression.
This study identifies Fgf8 as a gene essential for gastrulation
and shows that signaling via FGF8 and/or FGF4 is required
for cell migration away from the primitive streak.
[Key Words: anterior visceral endoderm; cell migration; epithelial-to-mesenchymal transition; Fgf4; Fgf8; gastrulation; mouse embryo; neuroectoderm patterning; primitive streak]
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