Genetic redundancy of GATA factors in the extraembryonic trophoblast lineage ensures the progression of preimplantation and postimplantation mammalian development.
Development
; 144(5): 876-888, 2017 03 01.
Article
in En
| MEDLINE
| ID: mdl-28232602
ABSTRACT
GATA transcription factors are implicated in establishing cell fate during mammalian development. In early mammalian embryos, GATA3 is selectively expressed in the extraembryonic trophoblast lineage and regulates gene expression to promote trophoblast fate. However, trophoblast-specific GATA3 function is dispensable for early mammalian development. Here, using dual conditional knockout mice, we show that genetic redundancy of Gata3 with paralog Gata2 in trophoblast progenitors ensures the successful progression of both pre- and postimplantation mammalian development. Stage-specific gene deletion in trophoblasts reveals that loss of both GATA genes, but not either alone, leads to embryonic lethality prior to the onset of their expression within the embryo proper. Using ChIP-seq and RNA-seq analyses, we define the global targets of GATA2/GATA3 and show that they directly regulate a large number of common genes to orchestrate stem versus differentiated trophoblast fate. In trophoblast progenitors, GATA factors directly regulate BMP4, Nodal and Wnt signaling components that promote embryonic-extraembryonic signaling cross-talk, which is essential for the development of the embryo proper. Our study provides genetic evidence that impairment of trophoblast-specific GATA2/GATA3 function could lead to early pregnancy failure.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Placenta
/
Stem Cells
/
Trophoblasts
/
GATA2 Transcription Factor
/
GATA3 Transcription Factor
Limits:
Animals
/
Female
/
Humans
/
Pregnancy
Language:
En
Journal:
Development
Journal subject:
BIOLOGIA
/
EMBRIOLOGIA
Year:
2017
Type:
Article
Affiliation country:
United States