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Self-organization of a human organizer by combined Wnt and Nodal signalling

Author

Listed:
  • I. Martyn

    (The Rockefeller University
    The Rockefeller University)

  • T. Y. Kanno

    (The Rockefeller University)

  • A. Ruzo

    (The Rockefeller University)

  • E. D. Siggia

    (The Rockefeller University)

  • A. H. Brivanlou

    (The Rockefeller University)

Abstract

In amniotes, the development of the primitive streak and its accompanying ‘organizer’ define the first stages of gastrulation. Although these structures have been characterized in detail in model organisms, the human primitive streak and organizer remain a mystery. When stimulated with BMP4, micropatterned colonies of human embryonic stem cells self-organize to generate early embryonic germ layers1. Here we show that, in the same type of colonies, Wnt signalling is sufficient to induce a primitive streak, and stimulation with Wnt and Activin is sufficient to induce an organizer, as characterized by embryo-like sharp boundary formation, markers of epithelial-to-mesenchymal transition and expression of the organizer-specific transcription factor GSC. Moreover, when grafted into chick embryos, human stem cell colonies treated with Wnt and Activin induce and contribute autonomously to a secondary axis while inducing a neural fate in the host. This fulfils the most stringent functional criteria for an organizer, and its discovery represents a milestone in human embryology.

Suggested Citation

  • I. Martyn & T. Y. Kanno & A. Ruzo & E. D. Siggia & A. H. Brivanlou, 2018. "Self-organization of a human organizer by combined Wnt and Nodal signalling," Nature, Nature, vol. 558(7708), pages 132-135, June.
    • Handle: RePEc:nat:nature:v:558:y:2018:i:7708:d:10.1038_s41586-018-0150-y
    DOI: 10.1038/s41586-018-0150-y
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    Cited by:

    1. Feng Lin & Xia Li & Shiyu Sun & Zhongyi Li & Chenglin Lv & Jianbo Bai & Lin Song & Yizhao Han & Bo Li & Jianping Fu & Yue Shao, 2023. "Mechanically enhanced biogenesis of gut spheroids with instability-driven morphomechanics," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Haipeng Fu & Tingyu Wang & Xiaohui Kong & Kun Yan & Yang Yang & Jingyi Cao & Yafei Yuan & Nan Wang & Kehkooi Kee & Zhi John Lu & Qiaoran Xi, 2022. "A Nodal enhanced micropeptide NEMEP regulates glucose uptake during mesendoderm differentiation of embryonic stem cells," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Hyung Chul Lee & Nidia M. M. Oliveira & Cato Hastings & Peter Baillie-Benson & Adam A. Moverley & Hui-Chun Lu & Yi Zheng & Elise L. Wilby & Timothy T. Weil & Karen M. Page & Jianping Fu & Naomi Moris , 2024. "Regulation of long-range BMP gradients and embryonic polarity by propagation of local calcium-firing activity," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Seth Teague & Gillian Primavera & Bohan Chen & Zong-Yuan Liu & LiAng Yao & Emily Freeburne & Hina Khan & Kyoung Jo & Craig Johnson & Idse Heemskerk, 2024. "Time-integrated BMP signaling determines fate in a stem cell model for early human development," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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