XB-ART-15033
Proc Natl Acad Sci U S A
April 14, 1998;
95
(8):
4398-403.
Cooperation between the activin and Wnt pathways in the spatial control of organizer gene expression.
Abstract
The normal expression pattern of the Wnt responsive homeobox gene
Siamois is restricted to the dorso-vegetal region of the Xenopus
embryo. Because the Wnt signaling pathway (via beta-catenin) is active on the entire dorsal side of the early
embryo, we have asked why
Siamois expression is not seen in the dorsal
ectoderm. Only Wnt signaling, via activation of beta-catenin, can induce directly
Siamois, and signaling via the
SMAD1 (BMP2/4) or
SMAD2 (activin/Vg-1) pathways cannot. We now directly show that the
SMAD2 pathway can cooperate with the Wnt pathway to induce expression of
Siamois much more strongly than the Wnt pathway alone, in normal embryos. We demonstrate the significance of this cooperation in normal embryos by blocking the
SMAD2 signaling pathway with a dominant negative activin receptor. The activin dominant negative receptor blocks this cooperative effect and reduces the expression of
Siamois by threefold in early embryos. Furthermore, we find that this cooperative relationship between the
SMAD2 and Wnt pathways is reciprocal. Thus, in normal embryos, the Wnt pathway can enhance induction, by the SMAD 2 pathway, of the
organizer genes
Gsc and
Chd but not the pan-mesodermal marker genes
Xbra and
Eomes. We conclude that the Wnt and
SMAD2 signaling pathways cooperate to induce the expression of Spemann-
organizer specific genes and so help to localize their spatial expression.
PubMed ID:
9539748
PMC ID:
PMC22500
Article link:
Proc Natl Acad Sci U S A
Grant support:
[+]
Species referenced:
Xenopus laevis
Genes referenced:
chrd.1
eomes
gsc
sia1
smad1
smad2
tbxt
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