Distinct sequential cell behaviours direct primitive endoderm formation in the mouse blastocyst
Open accessAbstract
The first two lineages to differentiate from a pluripotent cell population during mammalian development are the extraembryonic trophectoderm (TE) and the primitive endoderm (PrE). Whereas the mechanisms of TE specification have been extensively studied, segregation of PrE and the pluripotent epiblast (EPI) has received comparatively little attention. A current model of PrE specification suggests PrE precursors exhibit an apparently random distribution within the inner cell mass of the early blastocyst and then segregate to their final position lining the cavity by the late blastocyst. We have identified platelet-derived growth factor receptor alpha (Pdgfrα) as an early-expressed protein that is also a marker of the later PrE lineage. By combining live imaging of embryos expressing a histone H2B-GFP fusion protein reporter under the control of Pdgfra regulatory elements with the analysis of lineage-specific markers, we investigated the events leading to PrE and EPI lineage segregation in the mouse, and correlated our findings using an embryo staging system based on total cell number. Before blastocyst formation, lineage-specific factors are expressed in an overlapping manner. Subsequently, a gradual progression towards a mutually exclusive expression of PrE- and EPI-specific markers occurs. Finally, cell sorting is achieved by a variety of cell behaviours and by selective apoptosis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ICM lineage divergence into EPI and PrE occurs at E3.5.
“The changes in DP and BP suggest ICM lineage divergence into EPI and PrE occurs at E3.5 consistent with previous analyses using limited markers20,21”
From The emergent landscape of the mouse gut endoderm at single-cell resolution (2019) · cites this paper as [20]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 31
- Andrae J Gallini R Betsholtz C 2008 Role of platelet-derived growth factors in physiology and medicine Genes Dev 22 1276 1312 18483217 PMC2732412
- Becker S Casanova J Grabel L 1992 Localization of endoderm-specific mRNAs in differentiating F9 embryoid bodies Mech Dev 37 3 12 1376612
- Chambers I Silva J Colby D Nichols J Nijmeijer B Robertson M Vrana J Jones K Grotewold L Smith A 2007 Nanog safeguards pluripotency and mediates germline development Nature 450 1230 1234 18097409
- Chazaud C Yamanaka Y Pawson T Rossant J 2006 Early lineage segregation between epiblast and primitive endoderm in mouse blastocysts through the Grb2-MAPK pathway Dev Cell 10 615 624 16678776
- Copp AJ 1978 Interaction between inner cell mass and trophectoderm of the mouse blastocyst. I A study of cellular proliferation J Embryol Exp Morphol 48 109 125 744943
- Dietrich JE Hiiragi T 2007 Stochastic patterning in the mouse pre-implantation embryo Development 134 4219 4231 17978007
- Gerbe F Cox B Rossant J Chazaud C 2008 Dynamic expression of Lrp2 pathway members reveals progressive epithelial differentiation of primitive endoderm in mouse blastocyst Dev Biol 313 594 602 18083160
- Hadjantonakis AK Papaioannou VE 2004 Dynamic in vivo imaging and cell tracking using a histone fluorescent protein fusion in mice BMC Biotechnol 4 33 15619330 PMC544401
- Hamazaki T Kehoe SM Nakano T Terada N 2006 The Grb2/Mek pathway represses Nanog in murine embryonic stem cells Mol Cell Biol 26 7539 7549 16908534 PMC1636849
- Hamilton TG Klinghoffer RA Corrin PD Soriano P 2003 Evolutionary divergence of platelet-derived growth factor alpha receptor signaling mechanisms Mol Cell Biol 23 4013 4025 12748302 PMC155222
- Hoch RV Soriano P 2003 Roles of PDGF in animal development Development 130 4769 4784 12952899
- Hu M Krause D Greaves M Sharkis S Dexter M Heyworth C Enver T 1997 Multilineage gene expression precedes commitment in the hemopoietic system Genes Dev 11 774 785 9087431
- Kanda T Sullivan KF Wahl GM 1998 Histone-GFP fusion protein enables sensitive analysis of chromosome dynamics in living mammalian cells Curr Biol 8 377 385 9545195
- Koutsourakis M Langeveld A Patient R Beddington R Grosveld F 1999 The transcription factor GATA6 is essential for early extraembryonic development Development 126 723 732 9895320
- Kunath T Arnaud D Uy GD Okamoto I Chureau C Yamanaka Y Heard E Gardner RL Avner P Rossant J 2005 Imprinted X-inactivation in extra-embryonic endoderm cell lines from mouse blastocysts Development 132 1649 1661 15753215
- Kurimoto K Yabuta Y Ohinata Y Ono Y Uno KD Yamada RG Ueda HR Saitou M 2006 An improved single-cell cDNA amplification method for efficient high-density oligonucleotide microarray analysis Nucleic Acids Res 34 e42 16547197 PMC1409679
- Laforge B Guez D Martinez M Kupiec JJ 2005 Modeling embryogenesis and cancer: an approach based on an equilibrium between the autostabilization of stochastic gene expression and the interdependence of cells for proliferation Prog Biophys Mol Biol 89 93 120 15826673
- Long JZ Lackan CS Hadjantonakis AK 2005 Genetic and spectrally distinct in vivo imaging: embryonic stem cells and mice with widespread expression of a monomeric red fluorescent protein BMC Biotechnol 5 20 15996270 PMC1192791
- Martin GR Evans MJ 1975 Differentiation of clonal lines of teratocarcinoma cells: formation of embryoid bodies in vitro Proc Natl Acad Sci USA 72 1441 1445 1055416 PMC432551
- Martinez-Arias AM Hayward P 2006 Filtering transcriptional noise during development: concepts and mechanisms Nat Rev Genet 7 34 44 16369570
- Murray P Edgar D 2001 The regulation of embryonic stem cell differentiation by leukaemia inhibitory factor (LIF) Differentiation 68 227 234 11776475
- Nagy AN Gertsentein M Vintersten K Behringer R 2003 Manipulating the mouse embryo: a laboratory manual 3 Cold Spring Harbor, NY Cold Spring Harbor Laboratory Press
- Niwa H Toyooka Y Shimosato D Strumpf D Takahashi K Yagi R Rossant J 2005 Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation Cell 123 917 929 16325584
- Papaioannou VE West JD 1981 Relationship between the parental origin of the X chromosomes, embryonic cell lineage and X chromosome expression in mice Genet Res 37 183 197 7262553
- Perea-Gomez A Meilhac SM Piotrowska-Nitsche K Gray D Collignon J Zernicka-Goetz M 2007 Regionalization of the mouse visceral endoderm as the blastocyst transforms into the egg cylinder BMC Dev Biol 7 96 17705827 PMC1978209
- Plusa B Hadjantonakis AK Gray D Piotrowska-Nitsche K Jedrusik A Papaioannou VE Glover DM Zernicka-Goetz M 2005 The first cleavage of the mouse zygote predicts the blastocyst axis Nature 434 391 395 15772664
- Ralston A Rossant J 2008 Cdx2 acts downstream of cell polarization to cell-autonomously promote trophectoderm fate in the early mouse embryo Dev Biol 313 614 629 18067887
- Rossant J Chazaud C Yamanaka Y 2003 Lineage allocation and asymmetries in the early mouse embryo Philos Trans R Soc Lond B Biol Sci 358 1341 1348 14511480 PMC1693231
- Singh AM Hamazaki T Hankowski KE Terada N 2007 A heterogeneous expression pattern for Nanog in embryonic stem cells Stem Cells 25 2534 2542 17615266
- Strumpf D Mao CA Yamanaka Y Ralston A Chawengsaksophak K Beck F Rossant J 2005 Cdx2 is required for correct cell fate specification and differentiation of trophectoderm in the mouse blastocyst Development 132 2093 2102 15788452
- Yamanaka Y Ralston A Stephenson RO Rossant J 2006 Cell and molecular regulation of the mouse blastocyst Dev Dyn 235 2301 2314 16773657
Cited by
Sorted by citations
Making a commitment: cell lineage allocation and axis patterning in the early mouse embryo
Arnold, S. J., & Robertson, E. J. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2618 · Cited by 816 · see citing works
The emergent landscape of the mouse gut endoderm at single-cell resolution
Nowotschin, S., Setty, M., Kuo, Y.-Y., Liu, V., Garg, V., Sharma, R., Simon, C. S., Saiz, N., Gardner, R., Boutet, S. C., et al. (2019) · Nature · doi:10.1038/s41586-019-1127-1 · Cited by 383 · see citing works
Self-citationMolotkov, A., Mazot, P., Brewer, J. R., Cinalli, R. M., & Soriano, P. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.05.004 · Cited by 177 · see citing works
Takaoka, K., Yamamoto, M., & Hamada, H. (2011) · Nature Cell Biology · doi:10.1038/ncb2251 · Cited by 127 · see citing works
The endoderm: a divergent cell lineage with many commonalities
Nowotschin, S., Hadjantonakis, A.-K., & Campbell, K. (2019) · Development · doi:10.1242/dev.150920 · Cited by 94 · see citing works
Self-citationBMP signaling induces visceral endoderm differentiation of XEN cells and parietal endoderm
Paca, A., Séguin, C. A., Clements, M., Ryczko, M., Rossant, J., Rodriguez, T. A., & Kunath, T. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2011.10.013 · Cited by 87 · see citing works
Artus, J., Douvaras, P., Piliszek, A., Isern, J., Baron, M. H., & Hadjantonakis, A.-K. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2011.10.015 · Cited by 83 · see citing works
Self-citationAthanasouli, P., Balli, M., De Jaime-Soguero, A., Boel, A., Papanikolaou, S., van der Veer, B. K., Janiszewski, A., Vanhessche, T., Francis, A., El Laithy, Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36914-1 · Cited by 31 · see citing works
Formation of the Murine Endoderm
Tremblay, K. D. (2010) · Progress in Molecular Biology and Translational Science · doi:10.1016/b978-0-12-381280-3.00001-4 · Cited by 21 · see citing works
- Authors
- Plusa, B., Piliszek, A., Frankenberg, S., Artus, J., & Hadjantonakis, A.-K.
- Affiliations
- Developmental Biology Program, Sloan-Kettering Institute, New York, USA.
- Polish Academy of Sciences (PL)
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2008-09-15
- Volume
- 135
- Issue
- 18
- Pages
- 3081-3091
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- PMC
- PMC2768606
- OpenAlex
- W2118208715
- Cited by
- 556
- References
- 0
- Citations by year
- 2026: 12 · 2025: 31 · 2024: 27 · 2023: 40 · 2022: 34 · 2021: 34 · 2020: 29 · 2019: 29 · 2018: 34 · 2017: 36 · 2016: 31 · 2015: 36 · 2014: 34 · 2013: 32 · 2012: 40
- FWCI
- 10.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- National Cancer Institute (P30CA008748)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD052115)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Keywords
- primitive endoderm, epiblast, lineage segregation, blastocyst, PDGFRA, cell sorting, apoptosis, trophectoderm, inner cell mass, embryo staging, mouse embryo
- MeSH terms
- Animals, Blastocyst, Cells, Endoderm, Female, Genetic Markers, Histones, Models, Biological, Pregnancy, Recombinant Fusion Proteins, Genes, Reporter, Cell Lineage, Receptor, Platelet-Derived Growth Factor alpha, Green Fluorescent Proteins, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
