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Interaction between Hhex and SOX13 modulates Wnt/TCF activity.

Vanessa Marfil¹, Marta Moya, Christophe E Pierreux

¹Unitat de Biologia Cellular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, Barcelona 08003, Spain.

The Journal of Biological Chemistry

|December 24, 2009

Summary

Hematopoietically expressed homeobox (Hhex) interacts with SRY-related high mobility group box transcription factor 13 (SOX13) to modulate Wnt/TCF pathway activity. This interaction is crucial for embryonic development, particularly liver development, by regulating gene expression.

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Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients

Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients

Published on: December 14, 2015

Area of Science:

Developmental Biology
Molecular Biology
Genetics

Background:

The Wnt/TCF pathway is essential for embryonic development, including liver formation.
Hhex (hematopoietically expressed homeobox) is a key homeodomain factor in endoderm-derived tissues.
Hhex's dual role as repressor/activator suggests context-dependent partner interactions.

Purpose of the Study:

To identify and characterize novel interaction partners of Hhex.
To elucidate the role of Hhex-SOX13 interaction in Wnt/TCF pathway regulation.
To understand the impact of this interaction on embryonic development.

Main Methods:

Yeast two-hybrid screening using mouse embryo library and Hhex N-terminal domain.
Co-immunoprecipitation and domain mapping to confirm Hhex-SOX13 interaction.
In vitro Wnt/TCF reporter assays and in vivo electroporation in mouse embryos.

Main Results:

SOX13 (SRY-related high mobility group box transcription factor 13) was identified as a Hhex interactor.
Hhex directly binds SOX13, displacing it from the TCF1 complex and blocking SOX13-mediated Wnt/TCF repression.
Hhex de-repressed Wnt/TCF signaling in cultured mouse embryonic endoderm.

Conclusions:

Hhex-SOX13 interaction is a novel mechanism for modulating Wnt/TCF pathway activity.
This interaction plays a significant role in controlling Wnt/TCF signaling during early embryogenesis.
The findings contribute to understanding the molecular basis of liver development and other Wnt/TCF-dependent processes.