Non-Canonical Maternal WNT4 Activates Canonical Zygotic WNT8C for Early Embryonic Development in Chicken

The proper regulation of signaling pathways, including WNT signaling, during early embryonic development is critical for whole-organism development. In particular, maternally enriched WNTs play critical roles in cell cleavage and axis formation through non-canonical and canonical pathways during early embryogenesis. However, early developmental processes related to maternal WNTs and their underlying mechanisms have remained unstudied in avian species. In this study, we investigated WNT signaling-mediated early development in the chicken embryo. We found that <i>WNT4</i> and <i>WNT6</i>, different ligands from other species, exhibited expression patterns consistent with maternal enrichment in chicken. The chemical inhibition of maternal WNT signaling in intrauterine embryos led to aberrant zygotic expression of <i>WNT8C</i>, which is important for primitive streak formation. Combined with in vitro functional studies, we demonstrated that <i>WNT4</i> increased <i>WNT8C</i> expression through the non-canonical JNK pathway and that <i>WNT8C</i> subsequently promoted the canonical β-catenin pathway. Our results indicate that maternal <i>WNT4</i> activates zygotic <i>WNT8C</i> and potentially regulates embryonic polarity in chicken.