ArticleDevelopment (Cambridge, England)2013
FGF4 is required for lineage restriction and salt-and-pepper distribution of primitive endoderm factors but not their initial expression in the mouse.
Article in Development (Cambridge, England), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
142 citing papers in PubMed, 1 synthesis or guideline pooled it, 292 citations in OpenAlex.
- Lineage Differentiation Markers as a Proxy for Embryo Viability in Farm Ungulates.Frontiers in veterinary science · 2021Pooled it
- The transcription factor THAP11 is a general regulator of early embryonic polarization.bioRxiv : the preprint server for biology · 2026Article
- FGF4 initiates X-chromosome inactivation via activating YY1 and prompting loss of pluripotency factors.The EMBO journal · 2026Article
- Loss of maternal PADI6 disrupts DNA methylation and genomic imprinting maintenance in late preimplantation mouse embryos.Epigenetics & chromatin · 2026Article
- Optimality as a framework for understanding developmental robustness.Trends in cell biology · 2026Review
- Optogenetic WNT signaling drives germ layer self-organization in a human gastruloid model.bioRxiv : the preprint server for biology · 2026Article
- Wnt/β-catenin signalling modulates the timing of cell fate decision making in the early mouse embryo.PloS one · 2026Article
- Insulin-like growth factor 1 receptor (Frontiers in cell and developmental biology · 2026Article
- A conserved function of EZH2-PRC2 in repression of primitive endoderm fate in mouse and human pluripotent cells.Stem cell reports · 2025Article
- 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
- Live imaging endogenous transcription factor dynamics reveals mechanisms of epiblast and primitive endoderm fate segregation.Current biology : CB · 2025Article
- The role of ASS1 in mouse embryonic stem cell differentiation into mesendoderm lineages.Stem cell research & therapy · 2025Article
- Suppression of ERK signalling promotes pluripotent epiblast in the human blastocyst.Nature communications · 2025Article
- Deletion of a single CTCF motif at the boundary of a chromatin domain with three FGF genes disrupts gene expression and embryonic development.Developmental cell · 2025Article
- Donor embryonic stem cells displace host cells of 8-cell-stage chimeras to the extra-embryonic lineages by spatial crowding and FGF4 signalling.Development (Cambridge, England) · 2025Article
- Uncovering candidate Nanog-Helper genes in early mouse embryo differentiation using differential entropy and network inference.Scientific reports · 2025Article
- Genomic locus of lncRNA-Gm26793 forms an inter-chromosomal interaction with Cubn to ensure proper stem cell differentiation in vitro and in vivo.Cell discovery · 2025Article
- Stem cell-based embryo models: a tool to study early human development.Science China. Life sciences · 2025Review
- Med12 cooperates with multiple differentiation signals to facilitate efficient lineage transitions in embryonic stem cells.Journal of cell science · 2025Article
- Origin, fate and function of extraembryonic tissues during mammalian development.Nature reviews. Molecular cell biology · 2025Review
82 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The emergence of pluripotent epiblast (EPI) and primitive endoderm (PrE) lineages within the inner cell mass (ICM) of the mouse blastocyst involves initial co-expression of lineage-associated markers followed by mutual exclusion and salt-and-pepper distribution of lineage-biased cells. Precisely how EPI and PrE cell fate commitment occurs is not entirely clear; however, previous studies in mice have implicated FGF/ERK signaling in this process. Here, we investigated the phenotype resulting from zygotic and maternal/zygotic inactivation of Fgf4. Fgf4 heterozygous blastocysts exhibited increased numbers of NANOG-positive EPI cells and reduced numbers of GATA6-positive PrE cells, suggesting that FGF signaling is tightly regulated to ensure specification of the appropriate numbers of cells for each lineage. Although the size of the ICM was unaffected in Fgf4 null mutant embryos, it entirely lacked a PrE layer and exclusively comprised NANOG-expressing cells at the time of implantation. An initial period of widespread EPI and PrE marker co-expression was however established even in the absence of FGF4. Thus, Fgf4 mutant embryos initiated the PrE program but exhibited defects in its restriction phase, when lineage bias is acquired. Consistent with this, XEN cells could be derived from Fgf4 mutant embryos in which PrE had been restored and these cells appeared indistinguishable from wild-type cells. Sustained exogenous FGF failed to rescue the mutant phenotype. Instead, depending on concentration, we noted no effect or conversion of all ICM cells to GATA6-positive PrE. We propose that heterogeneities in the availability of FGF produce the salt-and-pepper distribution of lineage-biased cells.
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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.