Hes6 is required for MyoD induction during gastrulation

Abstract

The specification of mesoderm into distinct compartments sharing the same lineage restricted fates is a crucial step occurring during gastrulation, and is regulated by morphogenic signals such as the FGF/MAPK and activin pathways. One target of these pathways is the transcription factor XmyoD, which in early gastrulation is expressed in the lateral and ventral mesoderm. Expression of the hairy/enhancer of split transcription factor hes6, is also restricted to lateral and ventral mesoderm in gastrula stage Xenopus embryos, leading us to investigate whether it has a role in XmyoD regulation. In vivo, Xhes6 is required for FGF-mediated induction of XmyoD expression but not for induction of early mesoderm. The WRPW domain of Xhes6, which binds Groucho family transcriptional co-regulators, is essential for the XmyoD-inducing activity of Xhes6. Two Groucho proteins, Xgrg2 and Xgrg4, are expressed in lateral and ventral mesoderm, and inhibit expression of XmyoD. Xhes6 binds both Xgrg2 and Xgrg4 and relieves their inhibition of XmyoD expression. We also find that lowering Xhes6 expression levels blocks normal myogenic differentiation at tail bud stage. We conclude that Xhes6 is essential for XmyoD induction and acts by relieving Groucho-mediated repression of gene expression.