NANOG is required to establish the competence for germ-layer differentiation in the basal tetrapod axolotl

Simpson, Luke A; Crowley, Darren; Forey, Teri; Acosta, Helena; Ferjentsik, Zoltan; Chatfield, Jodie; Payne, Alexander; Simpson, Benjamin S; Redwood, Catherine; Dixon, James E; Holmes, Nadine; Sang, Fei; Alberio, Ramiro; Loose, Matthew; Johnson, Andrew D

Abstract

Pluripotency defines the unlimited potential of individual cells of vertebrate embryos, from which all adult somatic cells and germ cells are derived. Understanding how the programming of pluripotency evolved has been obscured in part by a lack of data from lower vertebrates; in model systems such as frogs and zebrafish, the function of the pluripotency genes NANOG and POU5F1 have diverged. Here, we investigated how the axolotl ortholog of NANOG programs pluripotency during development. Axolotl NANOG is absolutely required for gastrulation and germ-layer commitment. We show that in axolotl primitive ectoderm (animal caps; ACs) NANOG and NODAL activity, as well as the epigenetic modifying enzyme DPY30, are required for the mass deposition of H3K4me3 in pluripotent chromatin. We also demonstrate that all 3 protein activities are required for ACs to establish the competency to differentiate toward mesoderm. Our results suggest the ancient function of NANOG may be establishing the competence for lineage differentiation in early cells. These observations provide insights into embryonic development in the tetrapod ancestor from which terrestrial vertebrates evolved. [Abstract copyright: Copyright: © 2023 Simpson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.]

Citation

Simpson, L. A., Crowley, D., Forey, T., Acosta, H., Ferjentsik, Z., Chatfield, J., Payne, A., Simpson, B. S., Redwood, C., Dixon, J. E., Holmes, N., Sang, F., Alberio, R., Loose, M., & Johnson, A. D. (2023). NANOG is required to establish the competence for germ-layer differentiation in the basal tetrapod axolotl. PLoS Biology, 21(6), Article e3002121. https://doi.org/10.1371/journal.pbio.3002121

• Journal Article Type: Article
• Acceptance Date: Apr 13, 2023
• Online Publication Date: Jun 14, 2023
• Publication Date: 2023
• Deposit Date: Sep 27, 2023
• Publicly Available Date: Oct 26, 2023
• Journal: PLoS Biology
• Print ISSN: 1544-9173
• Electronic ISSN: 1545-7885
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 21
• Issue: 6
• Article Number: e3002121
• DOI: https://doi.org/10.1371/journal.pbio.3002121
• Public URL: https://nottingham-repository.worktribe.com/output/22450131
• Publisher URL: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002121