An essential function of the mitogen‐activated protein kinase Erk2 in mouse trophoblast development
Open accessAbstract
The closely related mitogen-activated protein kinase isoforms extracellular signal-regulated kinase 1 (ERK1) and ERK2 have been implicated in the control of cell proliferation, differentiation and survival. However, the specific in vivo functions of the two ERK isoforms remain to be analysed. Here, we show that disruption of the Erk2 locus leads to embryonic lethality early in mouse development after the implantation stage. Erk2 mutant embryos fail to form the ectoplacental cone and extra-embryonic ectoderm, which give rise to mature trophoblast derivatives in the fetus. Analysis of chimeric embryos showed that Erk2 functions in a cell-autonomous manner during the development of extra-embryonic cell lineages. We also found that both Erk2 and Erk1 are widely expressed throughout early-stage embryos. The inability of Erk1 to compensate for Erk2 function suggests a specific function for Erk2 in normal trophoblast development in the mouse, probably in regulating the proliferation of polar trophectoderm cells.
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During development, ERK1 and ERK2 have divergent functions since ERK1 null mice are grossly viable and fertile while ERK2 null mice are embryonic lethal.
“During development, ERK1 and ERK2 have divergent functions since ERK1 null mice are grossly viable and fertile while ERK2 null mice are embryonic lethal7–9.”
From Conditional loss of ERK1 and ERK2 results in abnormal placentation and delayed parturition in the mouse (2019) · cites this paper as [8]
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 [8]
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 [8]
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- Authors
- Saba‐El‐Leil, M. K., Vella, F. D. J., Vernay, B., Voisin, L., Chen, L., Labrecque, N., Ang, S., & Meloche, S.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Montreal Clinical Research Institute (CA)
- Corresponding author
- Meloche, Sylvain
- Venue
- The EMBO Reports
- Published
- 2003-09-19
- Volume
- 4
- Issue
- 10
- Pages
- 964-968
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC1326397
- OpenAlex
- W2130044807
- Cited by
- 366
- References
- 28
- Citations by year
- 2026: 5 · 2024: 6 · 2023: 14 · 2022: 12 · 2021: 8 · 2020: 11 · 2019: 11 · 2018: 9 · 2017: 13 · 2016: 18 · 2015: 20 · 2014: 14 · 2013: 19 · 2012: 25
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- EMBO Reports (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Cancer Research Society
- Centre National de la Recherche Scientifique
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- ERK2, ERK1, mitogen-activated protein kinase, trophoblast development, ectoplacental cone, extraembryonic ectoderm, embryonic lethality, chimeric embryos, cell-autonomous function, mouse embryo
- MeSH terms
- Animals, Female, Isoenzymes, Morphogenesis, Embryo Implantation, Phenotype, Pregnancy, Trophoblasts, In Situ Hybridization, Mice, Knockout, Gene Targeting, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Mitogen-Activated Protein Kinase 3, Mice
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