Crucial roles ofFoxa2in mouse anterior–posterior axis polarization via regulation of anterior visceral endoderm-specific genes

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Abstract
Anterior visceral endoderm (AVE) plays essential roles with respect to anterior–posterior axis development in the early mouse embryo. To assess the genetic cascade involved in AVE formation, the cis-regulatory elements directing expression of vertebrateOtx2genes in the AVE were analyzed via generation of transgenic mice.Otx2expression in AVE is regulated directly by the forkhead transcription factor,Foxa2. Moreover,Foxa2is essential for expression of theWntantagonists,Dkk1andCerl, in visceral endoderm during the pre- to early streak stages; however,Foxa2appears to be dispensable for subsequentDkk1expression associated with forebrain induction. Thus, we propose thatFoxa2is crucial in early anterior–posterior axis polarization in terms of regulation of expression of AVE-specific genes. These findings provide profound insights into conserved roles ofFoxa2transcription factors in anterior specification throughout the evolution of the chordate body plan.