Evidence map›Paper›PMID 34569938›Full record

ArticleeLife2021

Human embryo polarization requires PLC signaling to mediate trophectoderm specification.

Meng Zhu, Marta Shahbazi, Angel Martin, Chuanxin Zhang, Berna Sozen, Mate Borsos, Rachel S Mandelbaum, Richard J Paulson, Matteo A Mole, Marga Esbert and 11 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

33 citing papers in PubMed, 62 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Origin and development of primary animal epithelia.BioEssays : news and reviews in molecular, cellular and developmental biology · 2024
    Review
  18. Review
  19. Review
  20. Article
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

21 authors at 10 institutions in 4 countries.

Meng ZhuMammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Cambridge, United Kingdom.ORCID https://orcid.org/0000-0001-6157-8840
Marta Shahbazi *Mammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Cambridge, United Kingdom.ORCID https://orcid.org/0000-0002-1599-5747
Angel Martin *IVIRMA Valencia, IVI Foundation, Valencia, Spain.
Chuanxin ZhangCenter for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.
Berna SozenDevelopmental Plasticity and Self-Organization Group, California Institute of Technology, Division of Biology and Biological Engineering, Pasadena, United States.
Mate BorsosCalifornia Institute of Technology, Division of Biology and Biological Engineering,, Pasadena, United States.
Rachel S MandelbaumUSC Fertility, University of Southern California, Keck School of Medicine, Los Angeles, United Kingdom.
Richard J PaulsonUSC Fertility, University of Southern California, Keck School of Medicine, Los Angeles, United Kingdom.
Matteo A MoleMammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Cambridge, United Kingdom.
Marga EsbertIVIRMA New Jersey, Basking Ridge, NJ, United States.
Shiny TitusIVIRMA New Jersey, Basking Ridge, NJ, United States.
Richard T ScottIVIRMA New Jersey, Basking Ridge, NJ, United States.
Alison CampbellCARE Fertility Group, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham, United Kingdom.
Simon FishelCARE Fertility Group, John Webster House, 6 Lawrence Drive, Nottingham Business Park, Nottingham, United Kingdom.
Viviana GradinaruMRC Laboratory of Molecular Biology. Francis Crick Avenue, Biomedical Campus., Cambridge, United Kingdom.ORCID https://orcid.org/0000-0001-5868-348X
Han ZhaoKey laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China.
Keliang WuCenter for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.
Zi-Jiang ChenCenter for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.ORCID https://orcid.org/0000-0001-6637-6631
Emre SeliIVIRMA New Jersey, Basking Ridge, NJ, United States.ORCID https://orcid.org/0000-0001-7464-8203
Maria J de Los SantosIVIRMA Valencia, IVI Foundation, Valencia, Spain.
Magdalena Zernicka GoetzMammalian Embryo and Stem Cell Group, University of Cambridge, Department of Physiology, Development and Neuroscience, Cambridge, United Kingdom.ORCID https://orcid.org/0000-0002-7004-2471
Shandong University · CNCalifornia Institute of Technology · USCARE Fertility · USUniversity of Southern California · USValencian Infertility Institute · ESHarvard University · USMRC Laboratory of Molecular Biology · GBThe Francis Crick Institute · GBUniversity of Cambridge · GBYale University · US

Funding

Medical Research Council MC_UP_1201/24Wellcome TrustWellcome Trust 207415/Z/17/Z
6 · The paper itself

Abstract

Apico-basal polarization of cells within the embryo is critical for the segregation of distinct lineages during mammalian development. Polarized cells become the trophectoderm (TE), which forms the placenta, and apolar cells become the inner cell mass (ICM), the founding population of the fetus. The cellular and molecular mechanisms leading to polarization of the human embryo and its timing during embryogenesis have remained unknown. Here, we show that human embryo polarization occurs in two steps: it begins with the apical enrichment of F-actin and is followed by the apical accumulation of the PAR complex. This two-step polarization process leads to the formation of an apical domain at the 8-16 cell stage. Using RNA interference, we show that apical domain formation requires Phospholipase C (PLC) signaling, specifically the enzymes PLCB1 and PLCE1, from the eight-cell stage onwards. Finally, we show that although expression of the critical TE differentiation marker GATA3 can be initiated independently of embryo polarization, downregulation of PLCB1 and PLCE1 decreases GATA3 expression through a reduction in the number of polarized cells. Therefore, apical domain formation reinforces a TE fate. The results we present here demonstrate how polarization is triggered to regulate the first lineage segregation in human embryos.

Indexed as

Body PatterningCell DifferentiationCell LineageCell PolarityActinsAdultEmbryo Culture TechniquesEmbryo, MammalianFemaleGATA3 Transcription FactorGene Expression Regulation, DevelopmentalGene Expression Regulation, EnzymologicHumansPhosphoinositide Phospholipase CPhospholipase C betaPregnancyActinsGATA3 protein, humanGATA3 Transcription FactorPhosphoinositide Phospholipase CPhospholipase C betaphospholipase C epsilonPLCB1 protein, humancell biologycell polaritydevelopmental biologyhuman embryopreimplantation

Identifiers

PMID34569938
PMCPMC8514238
OpenAlexW3201797815

What OpenQuestion holds

Textmetadata
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.