Essential role for ERK2 mitogen‐activated protein kinase in placental development
Abstract
Background: Extracellular signal‐regulated kinase 2 (ERK2) has been implicated in cell proliferation, differentiation, and survival. However, its role in vivo remains to be determined. Results: Here we show that the targeted disruption of the mouse ERK2 gene results in embryonic lethality by E11.5 and severe abnormality of the placenta. In these animals, the labyrinthine layer of the placenta is very thin and few foetal blood vessels are observed. ERK2 mutants can be rescued by the transgenic expression of ERK2, demonstrating that these abnormalities are caused by ERK2‐deficiency. Although ERK2‐deficient fetuses are much smaller than wild‐type littermates, this seems to be secondary to malfunction of the placenta. When the placental defect is rescued by tetraploid‐aggregation, ERK2‐deficient foetuses grow as well as littermate controls. Conclusion: These observations indicate that ERK2 is essential for placental development and suggest that ERK2 in the trophoblast compartment may be indispensable for the vascularization of the labyrinth.
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Embryonic lethality of ERK2 null mice appears to be strain-specific and/or related to the design of the knockout allele; some reported failed early mesodermal differentiation while others reported mis-regulation of placental development.
“Embryonic lethality of the ERK2 null mice appears to be strain-specific and/or related to the design of the knockout allele; some having reported evidence of failed early mesodermal differentiation while others reporting mis-regulation of placental development10,11.”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [11]
Loss of ERK2 in null animals causes catastrophic defects early in mouse development or at later developmental stages in the mouse placenta leading to early fetal death.
“Other studies have shown that loss of ERK2 in null animals causes catastrophic defects early in mouse development10 or at later developmental stages in the mouse placenta leading to early fetal death8,11.”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [11]
All of these studies point to the specific importance of ERK2 during development since ERK1 did not compensate for the loss of ERK2.
“All of these studies point to the specific importance of ERK2 during development since in each experimental paradigm, ERK1 did not compensate for the loss of ERK2.”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [11]
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References 25 · Cited by 296
- Authors
- Hatano, N., Mori, Y., Oh‐hora, M., Kosugi, A., Fujikawa, T., Nakai, N., Niwa, H., Miyazaki, J., Hamaoka, T., & Ogata, M.
- Affiliations
- The University of Osaka (JP)
- Mie University (JP)
- Corresponding author
- Ogata, Masato
- ORCID
- Venue
- Genes to Cells
- Publisher
- Wiley
- Published
- 2003-09-30
- Volume
- 8
- Issue
- 11
- Pages
- 847-856
- ISSN
- 1356-9597 (ISSN-L)
- 1365-2443
- OpenAlex
- W2001585146
- Cited by
- 296
- References
- 25
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 7 · 2023: 11 · 2022: 9 · 2021: 14 · 2020: 12 · 2019: 13 · 2018: 15 · 2017: 13 · 2016: 12 · 2015: 16 · 2014: 9 · 2013: 10 · 2012: 18
- FWCI
- 11.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genes to Cells (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- ERK2, mitogen-activated protein kinase, placental development, trophoblast, placental labyrinth, placental vascularization, embryonic lethality, gene targeting, fetal growth restriction
- MeSH terms
- Animals, Female, Embryonic and Fetal Development, Genes, Lethal, Male, Mice, Inbred C57BL, Mice, Transgenic, Placenta, Pregnancy, Transfection, Trophoblasts, Immunoblotting, Gene Deletion, Mice, Knockout, Neovascularization, Physiologic, Mitogen-Activated Protein Kinase 1, Reverse Transcriptase Polymerase Chain Reaction, Mice
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