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The chromatin modifier Satb1 regulates cell fate through Fgf signalling in the early mouse embryo

Goolam, Mubeen and Zernicka-Goetz, Magdalena (2017) The chromatin modifier Satb1 regulates cell fate through Fgf signalling in the early mouse embryo. Development, 144 (8). pp. 1450-1461. ISSN 0950-1991. PMCID PMC5399666. doi:10.1242/dev.144139. https://resolver.caltech.edu/CaltechAUTHORS:20190405-170314644

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Abstract

The separation of embryonic from extra-embryonic tissues within the inner cell mass to generate the epiblast (EPI), which will form the new organism, from the primitive endoderm (PE), which will form the yolk sac, is a crucial developmental decision. Here, we identify a chromatin modifier, Satb1, with a distinct role in this decision. Satb1 is differentially expressed within 16-cell-stage embryos, with higher expression levels in the inner cell mass progenitor cells. Depleting Satb1 increases the number of EPI cells at the expense of PE. This phenotype can be rescued by simultaneous depletion of both Satb1 and Satb2, owing to their antagonistic effect on the pluripotency regulator Nanog. Consequently, increasing Satb1 expression leads to differentiation into PE and a decrease in EPI, as a result of the modulation of expression of several pluripotency- and differentiation-related genes by Satb1. Finally, we show that Satb1 is a downstream target of the Fgf signalling pathway, linking chromatin modification and Fgf signalling. Together, these results identify a role for Satb1 in the lineage choice between pluripotency and differentiation and further our understanding of early embryonic lineage segregation.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1242/dev.144139DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399666/PubMed CentralArticle
http://dev.biologists.org/lookup/doi/10.1242/dev.144139.supplementalPublisherSupporting Information
ORCID:
AuthorORCID
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2017. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. Received August 25, 2016. Accepted March 3, 2017. Published online April 11, 2017. We are grateful to our colleagues for advice during this project and for help with critical reading of this manuscript. We thank Meng Zhu for assistance with graphical representations. We are grateful to the Wellcome Trust Senior Research Fellowship to M.Z.-G. who funded this work (grant 098287). The funders had no role in the design, experimentation, analysis of the experiments, or preparation of the manuscript. Deposited in PMC for immediate release. The authors declare no competing or financial interests.
Funders:
Funding AgencyGrant Number
Wellcome Trust098287
Subject Keywords:Satb1, Epiblast, Primitive endoderm, Cell lineage specification, Preimplantation, Mouse
Issue or Number:8
PubMed Central ID:PMC5399666
DOI:10.1242/dev.144139
Record Number:CaltechAUTHORS:20190405-170314644
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190405-170314644
Official Citation:The chromatin modifier Satb1 regulates cell fate through Fgf signalling in the early mouse embryo Mubeen Goolam, Magdalena Zernicka-Goetz Development 2017 144: 1450-1461; doi: 10.1242/dev.144139
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94533
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:09 Apr 2019 18:21
Last Modified:16 Nov 2021 17:05

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