title: Interaction between Hhex and SOX13 modulates Wnt/TCF activity.
abstract: Fine-tuning of the Wnt/TCF pathway is crucial for multiple embryological processes, including liver development. Here we describe how the interaction between Hhex (hematopoietically expressed homeobox) and SOX13 (SRY-related high mobility group box transcription factor 13), modulates Wnt/TCF pathway activity. Hhex is a homeodomain factor expressed in multiple endoderm-derived tissues, like the liver, where it is essential for proper development. The pleiotropic expression of Hhex during embryonic development and its dual role as a transcriptional repressor and activator suggest the presence of different tissue-specific partners capable of modulating its activity and function. While searching for developmentally regulated Hhex partners, we set up a yeast two-hybrid screening using an E9.5-10.5 mouse embryo library and the N-terminal domain of Hhex as bait. Among the putative protein interactors, we selected SOX13 for further characterization. We found that SOX13 interacts directly with full-length Hhex, and we delineated the interaction domains within the two proteins. SOX13 is known to repress Wnt/TCF signaling by interacting with TCF1. We show that Hhex is able to block the SOX13-dependent repression of Wnt/TCF activity by displacing SOX13 from the SOX13 x TCF1 complex. Moreover, Hhex de-repressed the Wnt/TCF pathway in the ventral foregut endoderm of cultured mouse embryos electroporated with a SOX13-expressing plasmid. We conclude that the interaction between Hhex and SOX13 may contribute to control Wnt/TCF signaling in the early embryo.
authors.affiliation: Unitat de Biologia Cellular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, Barcelona 08003, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Marfil
authors.forename: Marta
authors.initials: M
authors.lastname: Moya
authors.forename: Christophe E
authors.initials: CE
authors.lastname: Pierreux
authors.forename: Jose V
authors.initials: JV
authors.lastname: Castell
authors.forename: Frédéric P
authors.initials: FP
authors.lastname: Lemaigre
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Real
authors.forename: Roque
authors.initials: R
authors.lastname: Bort
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004622:Embryo, Mammalian / Q000196:embryology; D047108:Embryonic Development / Q000502:physiology; D004707:Endoderm / Q000196:embryology; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000196:embryology*; D051379:Mice; D055755:SOXD Transcription Factors / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001324:Autoantigens; C078492:HHEX protein, human; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; C513080:Hhex protein, mouse; C496488:Hnf1a protein, mouse; D018398:Homeodomain Proteins; C491720:SOX13 protein, human; D055755:SOXD Transcription Factors; C110455:Sox13 protein, mouse; D014157:Transcription Factors; D051153:Wnt Proteins