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

  • EMBO J. 2025 Nov 24. doi: 10.1038/s44318-025-00643-6.
Yan-Yi Xing  #  1 ,  Ying Huang  #  2 ,  Tao Cheng  #  3 ,  Yi-Meng Tian  2 ,  Yang Dong  1 ,  Zi-Xin Jin  2 ,  Hai-Rong Pu  2 ,  Tao Luo  4 ,  Xiang Liu  2 ,  Hao-Nan Shen  2 ,  Jing Mo  5 ,  Jun Ma  2 ,  Jun-Feng Ji  4 ,  Peng-Fei Xu  6  7
Affiliations
  • 1. Women's Hospital, and Institute of Genetics, Zhejiang University School of Medicine, 310006, Hangzhou, Zhejiang, China.
  • 2. Center for Genetic Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, Zhejiang University, 322000, Yiwu, Zhejiang, China.
  • 3. Women's Hospital, and Institute of Genetics, Zhejiang University School of Medicine, 310006, Hangzhou, Zhejiang, China. [email protected].
  • 4. Center of Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, 310058, Hangzhou, Zhejiang, China.
  • 5. Department of Immunology, School of Basic Medicine, Guizhou Medical University, 561113, Guiyang, Guizhou, China.
  • 6. Women's Hospital, and Institute of Genetics, Zhejiang University School of Medicine, 310006, Hangzhou, Zhejiang, China. [email protected].
  • 7. Center for Genetic Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, Zhejiang University, 322000, Yiwu, Zhejiang, China. [email protected].
  • # Contributed equally.
PMID: 41286028 DOI: 10.1038/s44318-025-00643-6
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.

Keywords
BMP4; Human Pluripotent Stem Cells; Morphogenesis; Ventral-caudal Organizer; Zebrafish Explant.
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