title: The chromatin modifier Satb1 regulates cell fate through Fgf signalling in the early mouse embryo.
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.
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
authors.forename: Mubeen
authors.initials: M
authors.lastname: Goolam
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK mz205@cam.ac.uk.
authors.forename: Magdalena
authors.identifier: 0000-0002-7004-2471
authors.initials: M
authors.lastname: Zernicka-Goetz
mesh_terms: D000818:Animals; D002452:Cell Count; D019070:Cell Lineage / Q000235:genetics; D002843:Chromatin / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics; D004707:Endoderm / Q000166:cytology; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005855:Germ Layers / Q000166:cytology; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010641:Phenotype; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D002843:Chromatin; D036961:Matrix Attachment Region Binding Proteins; D034741:RNA, Small Interfering; C501473:SATB2 protein, mouse; C469541:Satb1 protein, mouse; D014157:Transcription Factors; D005346:Fibroblast Growth Factors
keywords: Cell lineage specification; Epiblast; Mouse; Preimplantation; Primitive endoderm; Satb1