In vertebrates, the neural induction requires the inhibition of BMP signals by dorsal organizer-derived antagonists. However, the underlying mechanism is not completely understood. Here, using zebrafish as a model, we show that ADNP2 orthologs adnp2a and adnp2b are required for proper neural induction in gastrulating embryos. Deficiency of adnp2 causes deficits in neuroectoderm specification, showing reduced expression of both anterior and posterior neural markers. Adnp2 functions as a transcriptional repressor, and directly occupies and suppresses the BMP-related ved/vent/vox homeobox genes, thereby excluding their expression from dorsal territories including the dorsal mesoderm and presumptive neural plate. adnp2-deficient larvae display aberrant behavioral alterations, which can be partially rescued by the administration of BMP antagonists Dorsomorphin or dnBmpr1 mRNAs. Our findings in zebrafish model reveal an indirect role of Adnp2 in neuroectoderm formation by antagonizing the activities of BMP-related ventralizing genes, which will be useful for understanding neural disorders caused by ADNP2 dysfunction in human.
Wang et al. (Fri,) studied this question.