Zfp281 is essential for mouse epiblast maturation through transcriptional and epigenetic control of Nodal signaling
- Icahn School of Medicine at Mount Sinai, United States
- Memorial Sloan Kettering Cancer Center, United States
Abstract
Pluripotency is defined by a cell's potential to differentiate into any somatic cell type. How pluripotency is transited during implantation, followed by lineage specification and establishment of the basic body plan is poorly understood. Here we report the transcription factor Zfp281 functions in the exit from naive pluripotency occurring coincident with pre-to-post-implantation mouse embryonic development. By characterizing Zfp281 mutant phenotypes and identifying Zfp281 gene targets and protein partners in developing embryos and cultured pluripotent stem cells, we establish critical roles for Zfp281 in activating components of the Nodal signaling pathway and lineage-specific genes. Mechanistically, Zfp281 cooperates with histone acetylation and methylation complexes at target gene enhancers and promoters to exert transcriptional activation and repression, as well as epigenetic control of epiblast maturation leading up to anterior-posterior axis specification. Our study provides a comprehensive molecular model for understanding pluripotent state progression in vivo during mammalian embryonic development.
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Article and author information
Author details
Anna-Katerina Hadjantonakis
Funding
National Institutes of Health (R01-GM095942)
- Jianlong Wang
National Institutes of Health (R21-HD087722)
- Jianlong Wang
New York State Department of Health (C028103)
- Jianlong Wang
New York State Department of Health (C028121)
- Jianlong Wang
National Institutes of Health (R01-DK084391)
- Anna-Katerina Hadjantonakis
National Institutes of Health (P30-CA008748)
- Anna-Katerina Hadjantonakis
New York State Department of Health (C029568)
- Anna-Katerina Hadjantonakis
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All mice used in this study were maintained in accordance with the guidelines of the Memorial Sloan Kettering Cancer Center (MSKCC) Institutional Animal Care and Use Committee (IACUC) under protocol number 03-12-017 (PI Hadjantonakis).
Reviewing Editor
- Marianne Bronner, California Institute of Technology, United States
Publication history
- Received: November 6, 2017
- Accepted: November 17, 2017
- Accepted Manuscript published: November 23, 2017 (version 1)
- Version of Record published: November 30, 2017 (version 2)
Copyright
© 2017, Huang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Zfp281 is essential for mouse epiblast maturation through transcriptional and epigenetic control of Nodal signaling
eLife 6:e33333.
https://doi.org/10.7554/eLife.33333
Further reading
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- Developmental Biology
- Evolutionary Biology
Development of tooth shape is regulated by the enamel knot signalling centre, at least in mammals. Fgf signalling regulates differential proliferation between the enamel knot and adjacent dental epithelia during tooth development, leading to formation of the dental cusp. The presence of an enamel knot in non-mammalian vertebrates is debated given differences in signalling. Here, we show the conservation and restriction of fgf3, fgf10, and shh to the sites of future dental cusps in the shark (Scyliorhinus canicula), whilst also highlighting striking differences between the shark and mouse. We reveal shifts in tooth size, shape, and cusp number following small molecule perturbations of canonical Wnt signalling. Resulting tooth phenotypes mirror observed effects in mammals, where canonical Wnt has been implicated as an upstream regulator of enamel knot signalling. In silico modelling of shark dental morphogenesis demonstrates how subtle changes in activatory and inhibitory signals can alter tooth shape, resembling developmental phenotypes and cusp shapes observed following experimental Wnt perturbation. Our results support the functional conservation of an enamel knot-like signalling centre throughout vertebrates and suggest that varied tooth types from sharks to mammals follow a similar developmental bauplan. Lineage-specific differences in signalling are not sufficient in refuting homology of this signalling centre, which is likely older than teeth themselves.
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- Developmental Biology
- Evolutionary Biology
The tooth shape of sharks and mice are regulated by a similar signaling center despite their teeth having very different geometries.
