Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2.
The mouse blastocyst and stem cells derived from its tissue lineages provide a unique genetic system for examining the establishment and loss of pluripotency. The transcription factor Cdx2 plays a central role by repressing pluripotency genes, such as Oct4, and promoting extraembryonic trophoblast fate at the blastocyst stage. However, genetic evidence has suggested that Cdx2 does not work alone in the trophoblast lineage. We have used bioinformatic and functional genomic strategies to identify the transcription factor Gata3 as a trophoblast factor. We show Gata3 to be capable of inducing trophoblast fate in embryonic stem cells and driving trophoblast differentiation in trophoblast stem cells. In addition, Cdx2 is not required for Gata3-induced expression of a subset of trophoblast genes in embryonic stem cells. We show that Gata3 is coexpressed with Cdx2 in the blastocyst, but this does not depend on Cdx2. In the embryo, expression of Gata3, like that of Cdx2, depends on Tead4, and the expression of both factors becomes restricted to trophoblast by a mechanism that does not initially rely on Oct4. These observations suggest that Gata3 and Cdx2 can act in parallel pathways downstream of Tead4 to induce the expression of common and independent targets in the trophoblast lineage, whereas Oct4 is required for continued repression of trophoblast fate in the embryonic lineage.
Ralston
Amy
A
Program in Developmental and Stem Cell Biology, Hospital for Sick Children Research Institute, MARS Building, Toronto Medical Discovery Tower, Toronto, ON M5G 1L7, Canada.
Cox
Brian J
BJ
Nishioka
Noriyuki
N
Sasaki
Hiroshi
H
Chea
Evelyn
E
Rugg-Gunn
Peter
P
Guo
Guoji
G
Robson
Paul
P
Draper
Jonathan S
JS
Rossant
Janet
J
D000818:Animals; D001755:Blastocyst / Q000166:cytology; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology; D004627:Embryonic Induction / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology; D005260:Female; D050990:GATA3 Transcription Factor / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000502:physiology*; D051379:Mice; D009124:Muscle Proteins / Q000502:physiology*; D050814:Octamer Transcription Factor-3 / Q000502:physiology*; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000502:physiology*; D014327:Trophoblasts / Q000166:cytology*
D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; D018398:Homeodomain Proteins; D009124:Muscle Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D000091262:TEA Domain Transcription Factors; C101204:Tead4 protein, mouse; D014157:Transcription Factors