ArticleDevelopmental biology2018
GATA6 phosphorylation by Erk1/2 propels exit from pluripotency and commitment to primitive endoderm.
Article in Developmental biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Oncogenic KRAS/ERK/JUNB signaling suppresses differentiation regulator GATA6 in pancreatic cancer.The Journal of clinical investigation · 2026Article
- Wnt/β-catenin signalling modulates the timing of cell fate decision making in the early mouse embryo.PloS one · 2026Article
- Lactate Promotes the Second Cell Fate Decision in Blastocysts by Prompting Primitive Endoderm Formation Through an Intercellular Positive Feedback Loop That Couples Paracrine FGF Signalling.Cell proliferation · 2025Article
- Why all MODY variants in transcription factor genes are dominantly inherited.Frontiers in genetics · 2025Article
- AI-powered simulation-based inference of a genuinely spatial-stochastic gene regulation model of early mouse embryogenesis.PLoS computational biology · 2024Article
- Optimization of Cas12a for multiplexed genome-scale transcriptional activation.Cell genomics · 2023Article
- Retention of ERK in the cytoplasm mediates the pluripotency of embryonic stem cells.Stem cell reports · 2023Article
- Journey of the mouse primitive endoderm: from specification to maturation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Review
- Early developmental plasticity enables the induction of an intermediate extraembryonic cell state.Science advances · 2022Article
- Paracrine interactions through FGFR1 and FGFR2 receptors regulate the development of preimplantation mouse chimaeric embryo.Open biology · 2022Article
- A pendulum of induction between the epiblast and extra-embryonic endoderm supports post-implantation progression.Development (Cambridge, England) · 2022Article
- GATA6 is predicted to regulate DNA methylation in an in vitro model of human hepatocyte differentiation.Communications biology · 2022Article
- Capturing Pluripotency and Beyond.Cells · 2021Review
- Environmental Exposures around Conception: Developmental Pathways Leading to Lifetime Disease Risk.International journal of environmental research and public health · 2021Review
- Dynamic conversion of cell sorting patterns in aggregates of embryonic stem cells with differential adhesive affinity.BMC developmental biology · 2021Article
- Cell-Cycle-Dependent ERK Signaling Dynamics Direct Fate Specification in the Mammalian Preimplantation Embryo.Developmental cell · 2020Article
- Article
- A Novel STAT3-Mediated GATA6 Pathway Contributes toOxidative medicine and cellular longevity · 2020Article
- The transition from local to global patterns governs the differentiation of mouse blastocysts.PloS one · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The transcription factor GATA6 and the Fgf/Ras/MAPK signaling pathway are essential for the development of the primitive endoderm (PrE), one of the two lineages derived from the pluripotent inner cell mass (ICM) of mammalian blastocysts. A mutant mouse line in which Gata6-coding exons are replaced with H2BGFP (histone H2B Green Fluorescence Protein fusion protein) was developed to monitor Gata6 promoter activity. In the Gata6-H2BGFP heterozygous blastocysts, the ICM cells that initially had uniform GFP fluorescence signal at E3.5 diverged into two populations by the 64-cell stage, either as the GFP-high PrE or the GFP-low epiblasts (Epi). However in the GATA6-null blastocysts, the originally moderate GFP expression subsided in all ICM cells, indicating that the GATA6 protein is required to maintain its own promoter activity during PrE linage commitment. In embryonic stem cells, expressed GATA6 was shown to bind and activate the Gata6 promoter in PrE differentiation. Mutations of a conserved serine residue (S264) for Erk1/2 phosphorylation in GATA6 protein drastically impacted its ability to activate its own promoter. We conclude that phosphorylation of GATA6 by Erk1/2 compels exit from pluripotent state, and the phosphorylation propels a GATA6 positive feedback regulatory circuit to compel PrE differentiation. Our findings resolve the longstanding question on the dual requirements of GATA6 and Ras/MAPK pathway for PrE commitment of the pluripotent ICM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.