In vitro characterization of the human segmentation clock

Margarete Diaz-Cuadros, Daniel E. Wagner, Christoph Budjan, Alexis Hubaud, Oscar A. Tarazona, Sophia Donelly, Arthur Michaut, Ziad Al Tanoury, Kumiko Yoshioka-Kobayashi, Yusuke Niino, Ryoichiro Kageyama, Atsushi Miyawaki, Jonathan Touboul and Olivier Pourquié ()
Additional contact information
Margarete Diaz-Cuadros: Harvard Medical School
Daniel E. Wagner: Harvard Medical School
Christoph Budjan: Harvard Medical School
Alexis Hubaud: Harvard Medical School
Oscar A. Tarazona: Harvard Medical School
Sophia Donelly: Harvard Medical School
Arthur Michaut: Harvard Medical School
Ziad Al Tanoury: Harvard Medical School
Kumiko Yoshioka-Kobayashi: Kyoto University
Yusuke Niino: RIKEN Center for Brain Science
Ryoichiro Kageyama: Kyoto University
Atsushi Miyawaki: RIKEN Center for Brain Science
Jonathan Touboul: Brandeis University
Olivier Pourquié: Harvard Medical School

Nature, 2020, vol. 580, issue 7801, 113-118

Abstract: Abstract The segmental organization of the vertebral column is established early in embryogenesis, when pairs of somites are rhythmically produced by the presomitic mesoderm (PSM). The tempo of somite formation is controlled by a molecular oscillator known as the segmentation clock1,2. Although this oscillator has been well-characterized in model organisms1,2, whether a similar oscillator exists in humans remains unknown. Genetic analyses of patients with severe spine segmentation defects have implicated several human orthologues of cyclic genes that are associated with the mouse segmentation clock, suggesting that this oscillator might be conserved in humans3. Here we show that human PSM cells derived in vitro—as well as those of the mouse4—recapitulate the oscillations of the segmentation clock. Human PSM cells oscillate with a period two times longer than that of mouse cells (5 h versus 2.5 h), but are similarly regulated by FGF, WNT, Notch and YAP signalling5. Single-cell RNA sequencing reveals that mouse and human PSM cells in vitro follow a developmental trajectory similar to that of mouse PSM in vivo. Furthermore, we demonstrate that FGF signalling controls the phase and period of oscillations, expanding the role of this pathway beyond its classical interpretation in ‘clock and wavefront’ models1. Our work identifying the human segmentation clock represents an important milestone in understanding human developmental biology.

Date: 2020
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DOI: 10.1038/s41586-019-1885-9

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