Hex acts with β-catenin to regulate anteroposterior patterning via a Groucho-related co-repressor and Nodal
2006
In Xenopus , the establishment of the anteroposterior axis involves
two key signalling pathways, canonical Wnt and Nodal-related TGFβ. There
are also a number of transcription factors that feedback upon these pathways.
The homeodomain protein Hex, an early marker of anterior positional
information, acts as a transcriptional repressor, suppressing induction and
propagation of the Spemman organiser while specifying anterior identity. We
show that Hex promotes anterior identity by amplifying the activity of
canonical Wnt signalling. Hex exerts this activity by inhibiting the
expression of Tle4 , a member of the Groucho family of transcriptional
co-repressors that we identified as a Hex target in embryonic stem (ES) cells
and Xenopus embryos. This Hex-mediated enhancement of Wnt signalling
results in the upregulation of the Nieuwkoop centre genes Siamois and
Xnr3 , and the subsequent increased expression of the anterior
endodermal marker Cerberus and other mesendodermal genes downstream
of Wnt signalling. We also identified Nodal as a Hex target in ES
cells. We demonstrate that in Xenopus , the Nodal-related genes
Xnr1 and Xnr2 , but not Xnr5 and Xnr6 , are
regulated directly by Hex. The identification of Nodal-related genes as Hex
targets explains the ability of Hex to suppress induction and propagation of
the organiser. Together, these results support a model in which Hex acts early
in development to reinforce a Wnt-mediated, Nieuwkoop-like signal to induce
anterior endoderm, and later in this tissue to block further propagation of
Nodal-related signals. The ability of Hex to regulate the same targets in both
Xenopus and mouse implies this model is conserved.
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