GATA6 levels modulate primitive endoderm cell fate choice and timing in the mouse blastocyst.
Cells of the inner cell mass (ICM) of the mouse blastocyst differentiate into the pluripotent epiblast or the primitive endoderm (PrE), marked by the transcription factors NANOG and GATA6, respectively. To investigate the mechanistic regulation of this process, we applied an unbiased, quantitative, single-cell-resolution image analysis pipeline to analyze embryos lacking or exhibiting reduced levels of GATA6. We find that Gata6 mutants exhibit a complete absence of PrE and demonstrate that GATA6 levels regulate the timing and speed of lineage commitment within the ICM. Furthermore, we show that GATA6 is necessary for PrE specification by FGF signaling and propose a model where interactions between NANOG, GATA6, and the FGF/ERK pathway determine ICM cell fate. This study provides a framework for quantitative analyses of mammalian embryos and establishes GATA6 as a nodal point in the gene regulatory network driving ICM lineage specification.
Duke Scholars
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- SOXF Transcription Factors
- Nanog Homeobox Protein
- Mice, Knockout
- Mice
- MAP Kinase Signaling System
- Homeodomain Proteins
- HMGB Proteins
- Gene Expression Regulation, Developmental
- GATA6 Transcription Factor
- Fibroblast Growth Factor 4
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- SOXF Transcription Factors
- Nanog Homeobox Protein
- Mice, Knockout
- Mice
- MAP Kinase Signaling System
- Homeodomain Proteins
- HMGB Proteins
- Gene Expression Regulation, Developmental
- GATA6 Transcription Factor
- Fibroblast Growth Factor 4