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Foxh1 recruits Gsc to negatively regulate Mixl1 expression during early mouse development
Author(s) -
Izzi Luisa,
Silvestri Cristoforo,
von Both Ingo,
Labbé Etienne,
Zakin Lise,
Wrana Jeffrey L,
Attisano Liliana
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601753
Subject(s) - biology , microbiology and biotechnology , expression (computer science) , genetics , cancer research , programming language , computer science
Mixl1 is a member of the Mix/Bix family of paired‐like homeodomain proteins and is required for proper axial mesendoderm morphogenesis and endoderm formation during mouse development. Mix/Bix proteins are transcription factors that function in Nodal‐like signaling pathways and are themselves regulated by Nodal. Here, we show that Foxh1 forms a DNA‐binding complex with Smads to regulate transforming growth factor β (TGFβ)/Nodal‐dependent Mixl1 gene expression. Whereas Foxh1 is commonly described as a transcriptional activator, we observed that Foxh1 ‐null embryos exhibit expanded and enhanced Mixl1 expression during gastrulation, indicating that Foxh1 negatively regulates expression of Mixl1 during early mouse embryogenesis. We demonstrate that Foxh1 associates with the homeodomain‐containing protein Goosecoid (Gsc), which in turn recruits histone deacetylases to repress Mixl1 gene expression. Ectopic expression of Gsc in embryoid bodies represses endogenous Mixl1 expression and this effect is dependent on Foxh1. As Gsc is itself induced in a Foxh1‐dependent manner, we propose that Foxh1 initiates positive and negative transcriptional circuits to refine cell fate decisions during gastrulation.