BMP4 initiates and patterns ventral-caudal structures in zebrafish and human pluripotent stem cell aggregates
摘要
The formation of body axes is a key developmental milestone in vertebrate embryos and is guided by specialized groups of cells known as organizers. The molecular nature of organizers has been extensively investigated across the vertebrate kingdom; however, the minimal conditions and factors sufficient to guide embryogenesis and organogenesis—particularly in humans—remain incompletely understood. Here, we show that BMP4 alone, when administered at an appropriate dosage, is sufficient to induce the formation of an organizer for ventral–caudal-like structure (VCLS) formation. This organizer directs endoderm-deficient ventral–caudal cell fate specification and morphogenesis in zebrafish embryos. In 3D human pluripotent stem cell (hPSC) aggregates, BMP4 can induce an elongated embryonic structure that is characterized by ventral–caudal cell fates. Importantly, hPSCs instructed by BMP4 are sufficient to induce a secondary posterior axis when grafted into the animal pole of the zebrafish embryo. Our study thus uncovers BMP4 as the inducer for the formation of a ventral–caudal organizer in the vertebrate embryo.