HNF3β and Lim1 interact in the visceral endoderm to regulate primitive streak formation and anterior-posterior polarity in the mouse embryo

Recent embryological and genetic experiments have suggested that the anterior visceral endoderm and the anterior primitive streak of the early mouse gastrula function as head- and trunk-organising centers, respectively. Here, we report that HNF3 beta and Lim1 are coexpressed in both organising centers suggesting synergistic roles of these genes in regulating organiser functions and hence axis development in the mouse embryo. To investigate this possibility, we generated compound HNF3 beta and Lim1 mutant embryos. An enlarged primitive streak and a lack of axis formation were observed in HNF3 beta(-/-);Lim1(-/-), but not in single homozygous mutant embryos. Chimera experiments indicate that the primary defect in these double homozygous mutants is due to loss of activity of HNF3 beta and Lim1 in the visceral endoderm, Altogether, these data provide evidence that these genes function synergistically to regulate organiser activity of the anterior visceral endoderm, Moreover, HNF3 beta(-/-); Lim1(-/-) mutant embryos also exhibit defects in mesoderm patterning that are likely due to lack of specification of anterior primitive streak cells.