Early Lineage Segregation between Epiblast and Primitive Endoderm in Mouse Blastocysts through the Grb2-MAPK Pathway
Open accessAbstract
It has been thought that early inner cell mass (ICM) is a homogeneous population and that cell position in the ICM leads to the formation of two lineages, epiblast (EPI) and primitive endoderm (PE), by E4.5. Here, however, we show that the ICM at E3.5 is already heterogeneous. The EPI- and PE-specific transcription factors, Nanog and Gata6, were expressed in the ICM in a random "salt and pepper" pattern, as early as E3.5, in a mutually exclusive manner. Lineage tracing showed predominant lineage restriction of single ICM cells at E3.5 to either lineage. In embryos lacking Grb2 where no PE forms, Gata6 expression was lost and all ICM cells were Nanog positive. We propose a model in which the ICM develops as a mosaic of EPI and PE progenitors at E3.5, dependent on Grb2-Ras-MAP kinase signaling, followed by later segregation of the progenitors into the appropriate cell layers.
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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 [21]
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- Authors
- Chazaud, C., Yamanaka, Y., Pawson, T., & Rossant, J.
- Affiliations
- Mount Sinai Hospital (CA)
- Corresponding author
- Rossant, Janet
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 10
- Issue
- 5
- Pages
- 615-624
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W2110737932
- Cited by
- 898
- References
- 0
- Citations by year
- 2026: 19 · 2025: 36 · 2024: 28 · 2023: 48 · 2022: 44 · 2021: 46 · 2020: 39 · 2019: 40 · 2018: 47 · 2017: 54 · 2016: 49 · 2015: 44 · 2014: 55 · 2013: 67 · 2012: 72
- FWCI
- 13.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2634 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- 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
- epiblast, primitive endoderm, inner cell mass, lineage segregation, Grb2, MAPK signaling, Ras signaling, Nanog, GATA6, lineage tracing, mouse blastocyst, cell fate specification
- MeSH terms
- Nanog Homeobox Protein, Animals, Blastocyst, Blastomeres, Cell Aggregation, DNA-Binding Proteins, Endoderm, Models, Biological, Morula, RNA, Messenger, Signal Transduction, Homeodomain Proteins, Gene Expression Regulation, Developmental, Cell Lineage, Receptor Protein-Tyrosine Kinases, Mitogen-Activated Protein Kinases, Cell Size, GATA6 Transcription Factor, Mice, GRB2 Adaptor Protein
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