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

Published version
Peer-reviewed

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Authors

Goolam, M 
Zernicka-Goetz, Magdalena  ORCID logo  https://orcid.org/0000-0002-7004-2471

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.

Description

Keywords

Satb1, epiblast, primitive endoderm, cell lineage specification, preimplantation, mouse

Journal Title

Development

Conference Name

Journal ISSN

0950-1991
1477-9129

Volume Title

144

Publisher

The Company of Biologists
Sponsorship
Wellcome Trust (098287/Z/12/Z)
We are grateful to the Wellcome Trust Senior Research Fellowship to M.Z.-G. who funded this work (grant 098287).