The primitive endoderm lineage of the mouse blastocyst: Sequential transcription factor activation and regulation of differentiation by Sox17
Open accessAbstract
Cells of the primitive endoderm (PrE) and the pluripotent epiblast (EPI), the two lineages specified within the inner cell mass (ICM) of the mouse blastocyst stage embryo, are segregated into adjacent tissue layers by the end of the preimplantation period. The PrE layer which emerges as a polarized epithelium adjacent to the blastocoel, with a basement membrane separating it from the EPI, has two derivatives, the visceral and parietal endoderm. In this study we have investigated the localization of two transcriptional regulators of the SOX family, SOX17 and SOX7, within the PrE and its derivatives. We noted that SOX17 was first detected in a salt-and-pepper distribution within the ICM, subsequently becoming restricted to the nascent PrE epithelium. This dynamic distribution of SOX17 resembled the localization of GATA6 and GATA4, two other PrE lineage-specific transcription factors. By contrast, SOX7 was only detected in PrE cells positioned in contact with the blastocoel, raising the possibility that these cells are molecularly distinct. Our observations support a model of sequential GATA6 > SOX17 > GATA4 > SOX7 transcription factor activation within the PrE lineage, perhaps correlating with the consecutive periods of cell lineage 'naïvete', commitment and sorting. Furthermore our data suggest that co-expression of SOX17 and SOX7 within sorted PrE cells could account for the absence of a detectable phenotype of Sox17 mutant blastocysts. However, analysis of implantation-delayed blastocysts, revealed a role for SOX17 in the maintenance of PrE epithelial integrity, with the absence of SOX17 leading to premature delamination and migration of parietal endoderm.
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Two PrE clusters at E3.5 represent nascent and more advanced populations during lineage maturation.
“We also identified two PrE clusters at E3.5, which we propose represent nascent (light blue) and more advanced (dark blue) populations during lineage maturation22”
From The emergent landscape of the mouse gut endoderm at single-cell resolution (2019) · cites this paper as [22]
These analyses provide precise ordering of markers during ICM lineage specification.
“These analyses provide precise ordering of markers during ICM lineage specification (Extended Data Fig. 5c)3,22,28.”
From The emergent landscape of the mouse gut endoderm at single-cell resolution (2019) · cites this paper as [22]
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- Authors
- Artus, J., Piliszek, A., & Hadjantonakis, A.-K.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Hadjantonakis, Anna-Katerina
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 350
- Issue
- 2
- Pages
- 393-404
- ISSN
- 0012-1606 (ISSN-L)
- PMC
- PMC3461954
- OpenAlex
- W2044039536
- Cited by
- 232
- References
- 52
- Citations by year
- 2026: 15 · 2025: 10 · 2024: 14 · 2023: 10 · 2022: 19 · 2021: 15 · 2020: 11 · 2019: 16 · 2018: 19 · 2017: 20 · 2016: 13 · 2015: 14 · 2014: 20 · 2013: 12 · 2012: 17
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (RO1-HD052115, RO1-DK084391)
- New York State Stem Cell Science
- Starr Foundation
- 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, mouse blastocyst, SOX17, SOX7, GATA6, GATA4, transcription factor activation, lineage specification, inner cell mass, parietal endoderm, visceral endoderm, blastocoel, epiblast, preimplantation embryo
- MeSH terms
- Animals, Blastocyst, Cell Differentiation, Cell Movement, Endoderm, Female, Male, Mice, Inbred ICR, Transcription Factors, Cell Polarity, Cell Lineage, HMGB Proteins, Mice, SOXF Transcription Factors
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