Maternal MAPK/Erk signaling regulates embryonic dorsal organizer formation in zebrafish

The dorsal organizer is induced by the maternal factor Huluwa (Hwa) primarily via activation of β-catenin signaling in vertebrate embryos. Although the mitogen-activated protein kinase (MAPK) cascade has been demonstrated to play a role in embryonic development, it remains unclear whether and how the maternal MAPK pathway regulates dorsal organizer formation. Here, we report the implication of maternal Erk1/Erk2 in the dorsal organizer formation of zebrafish embryos. Phosphorylated Erk1/2 (pErk1/2) is enriched in nuclei of presumptive dorsal blastomeres around the 1k-cell stage. Disruption of MAPK/Erk activation by chemical inhibition, maternal transgenic expression of dominant negative Erk2, or genetic mutation of maternal and zygotic erk1/2 genes could impair organizer formation and ventralize some embryos. Conversely, overexpression of the constitutively active form of Erk2 (caErk2) could restore the body axis in Mhwa or Mctnnb2 mutants and even induce two body axes. Mechanistically, Hwa promotes GSK3β degradation and thus stabilizes Ras protein, resulting in elevated pErk1/2 levels during early embryonic development. Intriguingly, maternal Erk1/2 signaling enhances hwa transcription via Jun and Fosab (also named Fos) during oogenesis. Our findings shed new light on the interplay between maternal Erk1/2 signaling and maternal Hwa for the induction of the dorsal organizer and body axis in the zebrafish.