Spatial and temporal patterns of ERK signaling during mouse embryogenesis
Abstract
Signaling between tissues is essential to form the complex,three-dimensional organization of an embryo. Because many receptor tyrosine kinases signal through the RAS-MAPK pathway, phosphorylated ERK can be used as an indicator of when and where signaling is active during development. Using whole-mount immunohistochemistry with antibodies specific to phosphorylated ERK1 and ERK2, we analyzed the location, timing, distribution, duration and intensity of ERK signaling during mouse embryogenesis (5-10.5 days postcoitum). Spatial and temporal domains of ERK activation were discrete with well-defined boundaries, indicating specific regulation of signaling in vivo. Prominent, sustained domains of ERK activation were seen in the ectoplacental cone, extra-embryonic ectoderm, limb buds, branchial arches, frontonasal process, forebrain, midbrain-hindbrain boundary, tailbud, foregut and liver. Transient activation was seen in neural crest, peripheral nervous system,nascent blood vessels, and anlagen of the eye, ear and heart. In the contiguous domains of ERK signaling, phospho-ERK staining was cytoplasmic with no sign of nuclear translocation. With few exceptions, the strongest domains of ERK activation correlated with regions of known or suspected fibroblast growth factor (FGF) signaling, and brief incubation with an inhibitor of the fibroblast growth factor receptor (FGFR) specifically diminished the phospho-ERK staining in these regions. Although many domains of ERK activation were FGFR-dependent, not all domains of FGF signaling were phospho-ERK positive. These studies identify key domains of sustained ERK signaling in the intact mouse embryo, give significant insight into the regulation of this signaling in vivo and pinpoint regions where downstream target genes can be sought.
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p-Erk participates in early embryonic endoderm foregut specification.
“phosphorylated Erks (p-Erk) participate in early embryonic endoderm foregut specification47”
From Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis (2024) · cites this paper as [47]
High dp-Erk distribution within embryonic foregut presupposes the critical function of BRAF/MAPK in the descendent tissue thyroid.
“Moreover, the high dp-Erk distribution within embryonic foregut presupposes the critical function of BRAF/MAPK in the descendent tissue thyroid, since the liver, another descendent tissue, also needs enough Erks for homeostasis47,51.”
From Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis (2024) · cites this paper as [47]
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- Authors
- Corson, L. B., Yamanaka, Y., Lai, K.-M. V., & Rossant, J.
- Affiliations
- Mount Sinai Hospital (CA)
- Corresponding author
- Rossant, Janet
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2003-10-01
- Volume
- 130
- Issue
- 19
- Pages
- 4527-4537
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2035422545
- Cited by
- 390
- References
- 64
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 11 · 2023: 5 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 19 · 2017: 16 · 2016: 15 · 2015: 26 · 2014: 19 · 2013: 17 · 2012: 21
- FWCI
- 10.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- ERK signaling, RAS/MAPK pathway, mouse embryo development, FGF signaling, fibroblast growth factor receptor, ectoplacental cone, extraembryonic ectoderm, neural crest, midbrain-hindbrain boundary, foregut, liver, limb bud, branchial arches, frontonasal process, tail bud, angiogenesis
- MeSH terms
- Animals, Embryo, Mammalian, Embryonic Structures, Enzyme Activation, Female, Embryonic and Fetal Development, Gestational Age, Morphogenesis, Phosphorylation, Pregnancy, Receptors, Fibroblast Growth Factor, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Embryonic Development, Mitogen-Activated Protein Kinase 3, Mice
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