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Vol. 15, No. 15, pp. 1998-2009, August 1, 2001
1 Department of Molecular Biology, Cell Biology, and
Biochemistry, Brown University, Providence, Rhode Island 02912, USA;
2 Cell and Developmental Biology Program, Fox Chase Cancer
Center, Philadelphia, Pennsylvania 19111, USA; 3 Department of
Cell Biology, Vanderbilt University Medical Center, Nashville,
Tennessee 37232, USA
Mesodermal signaling is critical for patterning the embryonic
endoderm into different tissue domains. Classical tissue transplant experiments in the chick and recent studies in the mouse indicated that
interactions with the cardiogenic mesoderm are necessary and sufficient
to induce the liver in the ventral foregut endoderm. Using molecular
markers and functional assays, we now show that septum transversum
mesenchyme cells, a distinct mesoderm cell type, are closely apposed to
the ventral endoderm and contribute to hepatic induction. Specifically,
using a mouse Bmp4 null mutation and an inhibitor of BMPs, we
find that BMP signaling from the septum transversum mesenchyme is
necessary to induce liver genes in the endoderm and to exclude a
pancreatic fate. BMPs apparently function, in part, by affecting the
levels of the GATA4 transcription factor, and work in parallel to FGF
signaling from the cardiac mesoderm. BMP signaling also appears
critical for morphogenetic growth of the hepatic endoderm into a liver
bud. Thus, the endodermal domain for the liver is specified by
simultaneous signaling from distinct mesodermal sources.
[Key Words: BMP; liver; mesoderm; endoderm; septum transversum]
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