Canonical Wnt and Nodal signaling are both required
for induction of the primitive streak (PS), which
guides organization of the early embryo. The Wnt
effector b-catenin is thought to function in these
early lineage specification decisions via transcriptional
activation of Nodal signaling. Here, we demonstrate
a broader role for b-catenin in PS formation by
analyzing its genome-wide binding in a human embryonic
stem cell model of PS induction. b-catenin
occupies regulatory regions in numerous PS and
neural crest genes, and direct interactions between
b-catenin and the Nodal effectors SMAD2/SMAD3
are required at these regions for PS gene activation.
Furthermore, OCT4 binding in proximity to these
sites is likewise required for PS induction, suggesting
a collaborative interaction between b-catenin and
OCT4. Induction of neural crest genes by b-catenin
is repressed by SMAD2/SMAD3, ensuring proper
lineage specification. This study provides mechanistic
insight into how Wnt signaling controls early
cell lineage decisions.