Cited by 55Developmental Biology and Gene RegulationFibroblast Growth Factor ResearchPluripotent Stem Cells Research

A Sprouty4 reporter to monitor FGF/ERK signaling activity in ESCs and mice

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Morgani, Sophie M., Saiz, Nestor, Garg, Vidur, Raina, Dhruv, Simon, Claire S., Kang, Minjung, Arias, Alfonso Martinez, Nichols, Jennifer +2 more·2018·Developmental Biology

Abstract

The FGF/ERK signaling pathway is highly conserved throughout evolution and plays fundamental roles during embryonic development and in adult organisms. While a plethora of expression data exists for ligands, receptors and pathway regulators, we know little about the spatial organization or dynamics of signaling in individual cells within populations. To this end we developed a transcriptional readout of FGF/ERK activity by targeting a histone H2B-linked Venus fluorophore to the endogenous locus of Spry4, an early pathway target, and generated Spry4 H2B-Venus embryonic stem cells (ESCs) and a derivative mouse line. The Spry4 H2B-Venus reporter was heterogeneously expressed within ESC cultures and responded to FGF/ERK signaling manipulation. In vivo, the Spry4 H2B-Venus reporter recapitulated the expression pattern of Spry4 and localized to sites of known FGF/ERK activity including the inner cell mass of the pre-implantation embryo and the limb buds, somites and isthmus of the post-implantation embryo. Additionally, we observed highly localized reporter expression within adult organs. Genetic and chemical disruption of FGF/ERK signaling, in vivo in pre- and post-implantation embryos, abrogated Venus expression establishing the reporter as an accurate signaling readout. This tool will provide new insights into the dynamics of the FGF/ERK signaling pathway during mammalian development.

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Authors
Morgani, S. M., Saiz, N., Garg, V., Raina, D., Simon, C. S., Kang, M., Arias, A. M., Nichols, J., Schröter, C., & Hadjantonakis, A.-K.
Affiliations
  • Memorial Sloan Kettering Cancer Center (US)
  • Max Planck Institute of Molecular Physiology (DE)
  • Wellcome/MRC Cambridge Stem Cell Institute (GB)
Corresponding author
Hadjantonakis, Anna-Katerina
Venue
Developmental Biology
Publisher
Elsevier BV
Published
2018-09
Volume
441
Issue
1
Pages
104-126
ISSN
0012-1606 (ISSN-L)
OpenAlex
W2810807384
Cited by
55
References
134
Citations by year
2026: 5 · 2025: 5 · 2024: 9 · 2023: 8 · 2022: 7 · 2021: 8 · 2020: 4 · 2019: 7 · 2018: 2
FWCI
1.87
Type
journal article
Language
en
Open access
Locations
  • Developmental Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Max Planck Digital Library (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion)
Funders
  • NIH (R01HD094868, R01DK084391, P30CA00874)
  • BBSRC Project (BB/M023370/1)
  • Wellcome Trust Sir Henry Wellcome Postdoctoral Fellowship (110151/Z/15/Z)
  • Starr Foundation Tri-Institutional Stem Cell Initiative
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords
SPRY4, embryonic stem cells, preimplantation embryo, postimplantation embryo, limb bud, somites, isthmus
MeSH terms
Mouse Embryonic Stem Cells, Animals, Embryo, Mammalian, Fibroblast Growth Factors, Nerve Tissue Proteins, MAP Kinase Signaling System, Organogenesis, Embryonic Development, Extracellular Signal-Regulated MAP Kinases, Mice, Cell Tracking

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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