Evidence map›Paper›PMID 25340657›Full record

ArticlePLoS genetics2014

HIPPO pathway members restrict SOX2 to the inner cell mass where it promotes ICM fates in the mouse blastocyst.

Eryn Wicklow, Stephanie Blij, Tristan Frum, Yoshikazu Hirate, Richard A Lang, Hiroshi Sasaki, Amy Ralston

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed, 1 pooled it
7.4field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

131 citing papers in PubMed, 1 synthesis or guideline pooled it, 252 citations in OpenAlex.

  1. Pooled it
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  16. Hippo signaling in mammalian reproduction.Reproduction (Cambridge, England) · 2025
    Review
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  18. Article
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71 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Eryn WicklowMolecular, Cell, and Developmental Biology, University of California Santa Cruz, Santa Cruz, California, United States of America.
Stephanie BlijMolecular, Cell, and Developmental Biology, University of California Santa Cruz, Santa Cruz, California, United States of America.
Tristan FrumMolecular, Cell, and Developmental Biology, University of California Santa Cruz, Santa Cruz, California, United States of America.
Yoshikazu HirateInstitute of Molecular Embryology and Genetics, Kumamoto University, Chuo-ku, Kumamoto, Japan.
Richard A LangDivision of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Hiroshi SasakiInstitute of Molecular Embryology and Genetics, Kumamoto University, Chuo-ku, Kumamoto, Japan.
Amy RalstonMolecular, Cell, and Developmental Biology, University of California Santa Cruz, Santa Cruz, California, United States of America.
University of California, Santa Cruz · USKumamoto University · JPCincinnati Children's Hospital Medical Center · US

Funding

Training Program/Molecular/Cell/Developmental BiologyT32GM008646 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI STROME, SUSAN · 1999 to 2018
$3.7M
Molecular Regulation of Cell Fate in Stem Cells and Early Mouse EmbryosR01GM104009 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI RALSTON, AMY · 2013 to 2018
$2.3M
Retinal Microglia and AngiogenesisR01EY021636 · NEI · CINCINNATI CHILDRENS HOSP MED CTR · PI LANG, RICHARD A. · 2012 to 2016
$1.9M
NEI NIH HHS R01 EY021636NIGMS NIH HHS R01 GM104009NIGMS NIH HHS R01GM104009NIGMS NIH HHS T32 GM008646
6 · The paper itself

Abstract

Pluripotent epiblast (EPI) cells, present in the inner cell mass (ICM) of the mouse blastocyst, are progenitors of both embryonic stem (ES) cells and the fetus. Discovering how pluripotency genes regulate cell fate decisions in the blastocyst provides a valuable way to understand how pluripotency is normally established. EPI cells are specified by two consecutive cell fate decisions. The first decision segregates ICM from trophectoderm (TE), an extraembryonic cell type. The second decision subdivides ICM into EPI and primitive endoderm (PE), another extraembryonic cell type. Here, we investigate the roles and regulation of the pluripotency gene Sox2 during blastocyst formation. First, we investigate the regulation of Sox2 patterning and show that SOX2 is restricted to ICM progenitors prior to blastocyst formation by members of the HIPPO pathway, independent of CDX2, the TE transcription factor that restricts Oct4 and Nanog to the ICM. Second, we investigate the requirement for Sox2 in cell fate specification during blastocyst formation. We show that neither maternal (M) nor zygotic (Z) Sox2 is required for blastocyst formation, nor for initial expression of the pluripotency genes Oct4 or Nanog in the ICM. Rather, Z Sox2 initially promotes development of the primitive endoderm (PE) non cell-autonomously via FGF4, and then later maintains expression of pluripotency genes in the ICM. The significance of these observations is that 1) ICM and TE genes are spatially patterned in parallel prior to blastocyst formation and 2) both the roles and regulation of Sox2 in the blastocyst are unique compared to other pluripotency factors such as Oct4 or Nanog.

Indexed as

AnimalsBlastocystBlastocyst Inner Cell MassCell DifferentiationCell LineageEmbryonic DevelopmentEmbryonic Stem CellsEndodermGene Expression Regulation, DevelopmentalHippo Signaling PathwayHomeodomain ProteinsMiceNanog Homeobox ProteinOctamer Transcription Factor-3Pluripotent Stem CellsProtein Serine-Threonine KinasesHomeodomain ProteinsNanog Homeobox ProteinNanog protein, mouseOctamer Transcription Factor-3Pou5f1 protein, mouseProtein Serine-Threonine KinasesSox2 protein, mouseSOXB1 Transcription Factors

Identifiers

PMID25340657
PMCPMC4207610
OpenAlexW2078035928

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.