# BMP4 initiates and patterns ventral-caudal structures in zebrafish and human pluripotent stem cell aggregates

## TL;DR

BMP4 can act as a signaling molecule to form posterior body structures in zebrafish and human stem cells, revealing a conserved mechanism across vertebrates.

## Contribution

BMP4 alone is shown to induce a ventral-caudal organizer in vertebrates, revealing a minimal and conserved signaling mechanism.

## Key findings

- BMP4 induces a ventral-caudal organizer in zebrafish embryos, directing cell fate and morphogenesis.
- BMP4-expressing human stem cells can form a secondary posterior axis when grafted into zebrafish embryos.
- BMP4 signaling creates ventral-caudal-like structures in human 3D stem cell aggregates in vitro.

## Abstract

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.

The vertebrate body’s posterior part forms through a complex interplay of signals emitted by specialized cells forming a so-called “organizer”. This study reveals that BMP4 alone is sufficient to create a “ventral-caudal organizer” that directs the development of posterior structures, pointing to a minimal, evolutionarily conserved signaling for building the posterior body plan across vertebrates.

Ectopic BMP4 in the zebrafish animal pole induces a secondary axis containing somites and a tailbud but lacking notochord and endoderm.These BMP4-induced structures recapitulate key aspects of gastrulation, somitogenesis, and anterior-posterior patterning of ventral-caudal tissues.Human pluripotent stem cells expressing BMP4 can organize a secondary caudal axis when transplanted into zebrafish embryos, demonstrating cross-species organizer activity.The BMP4 signaling center induces a ventral-caudal-like structure in human 3D pluripotent stem cell aggregates in vitro.

Ectopic BMP4 in the zebrafish animal pole induces a secondary axis containing somites and a tailbud but lacking notochord and endoderm.

These BMP4-induced structures recapitulate key aspects of gastrulation, somitogenesis, and anterior-posterior patterning of ventral-caudal tissues.

Human pluripotent stem cells expressing BMP4 can organize a secondary caudal axis when transplanted into zebrafish embryos, demonstrating cross-species organizer activity.

The BMP4 signaling center induces a ventral-caudal-like structure in human 3D pluripotent stem cell aggregates in vitro.

BMP4 induces formation of an organizer that orchestrates key aspects of gastrulation and somitogenesis.