BMP4 is sufficient to induce a caudal organizer

Abstract

The caudal part of a vertebrate embryo consists of somites, neural tube, lateral plate mesoderm derivatives and the tailbud. However, the minimal conditions and factors sufficient to induce the caudal region, particularly in humans, remain unresolved. Here, we show that BMP4 alone, when administered at appropriate dosage, is sufficient to induce the formation of an organizer for caudal induction. This organizer induces caudal cell fate specification and morphogenesis in zebrafish embryos. In 3D human pluripotent stem cells (hPSCs) aggregates, BMP4 can induce an elongated embryonic structure characterized by caudal fates. Importantly, hPSCs instructed by BMP4 are sufficient to induce a secondary caudal region when grafted into the animal pole of the zebrafish embryo. Our study thus uncovers BMP4 as the inducer in the formation of a caudal organizer in the vertebrate embryo. Significance statementWe demonstrate that BMP4 alone can induce the formation of a caudal organizer, a critical structure that guides the development of the caudal region in vertebrates. Using zebrafish embryos, embryonic explants, human pluripotent stem cell xenografts, and 3D human stem cell aggregates, we show that this organizer replicates morphogenesis and key differentiation pathways seen in natural development. Our findings uncover a novel role for BMP4 and define the minimal requirements for inducing this organizer, offering new insights into vertebrate development and potential applications in regenerative medicine.