EphrinB1/EphB3b Coordinate Bidirectional Epithelial-Mesenchymal Interactions Controlling Liver Morphogenesis and Laterality
Open accessAbstract
Positioning organs in the body often requires the movement of multiple tissues, yet the molecular and cellular mechanisms coordinating such movements are largely unknown. Here, we show that bidirectional signaling between EphrinB1 and EphB3b coordinates the movements of the hepatic endoderm and adjacent lateral plate mesoderm (LPM), resulting in asymmetric positioning of the zebrafish liver. EphrinB1 in hepatoblasts regulates directional migration and mediates interactions with the LPM, where EphB3b controls polarity and movement of the LPM. EphB3b in the LPM concomitantly repels hepatoblasts to move leftward into the liver bud. Cellular protrusions controlled by Eph/Ephrin signaling mediate hepatoblast motility and long-distance cell-cell contacts with the LPM beyond immediate tissue interfaces. Mechanistically, intracellular EphrinB1 domains mediate EphB3b-independent hepatoblast extension formation, while EpB3b interactions cause their destabilization. We propose that bidirectional short- and long-distance cell interactions between epithelial and mesenchyme-like tissues coordinate liver bud formation and laterality via cell repulsion.
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In zebrafish, emergence and positioning of hepatoblasts is accomplished by CCM, with ephrin signaling and hepatoblast filopodia mediating contacts between gut tube and mesodermal lineages.
“In zebrafish, emergence and positioning of hepatoblasts is accomplished by CCM, with ephrin signaling and hepatoblast filopodia mediating contacts between gut tube and mesodermal lineages”
From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Cayuso et al., 2016
The Results section, “Hepatoblasts Actively Migrate during Liver Budding” (page unavailable), describes coordinated hepatoblast movement into the liver bud, suggesting collective cell migration. The Discussion describes EphrinB1/EphB3b signaling and protrusions facilitating contacts between hepatoblasts and lateral plate mesoderm. However, the Introduction says hepatoblasts are specified by signals from the mesoderm; the paper does not establish that collective cell migration accomplishes their initial emergence. (LLM, conf=0.82)
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Daar, I. O., & Yoon, J. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736930143.793571582
Fagotto, F. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736581487.793576323
- Authors
- Cayuso, J., Dzementsei, A., Fischer, J. C., Karemore, G., Caviglia, S., Bartholdson, J., Wright, G. J., & Ober, E. A.
- Affiliations
- University of Copenhagen (DK)
- Wellcome Sanger Institute (GB)
- Corresponding author
- Ober, Elke A.
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 39
- Issue
- 3
- Pages
- 316-328
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC5107609
- OpenAlex
- W2551651295
- Cited by
- 46
- References
- 50
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 6 · 2019: 8 · 2018: 9 · 2017: 3 · 2016: 1
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Figshare (submittedVersion, cc-by)
- Wolverhampton Intellectual Repository and E-Theses (University of Wolverhampton) (submittedVersion, cc-by)
- Funders
- Medical Research Council (U117581329)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Danmarks Grundforskningsfond (DNRF116)
- Novo Nordisk Fonden (NNF15CC0018344)
- Wellcome Trust (098051)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- ephrin-B1, Eph/ephrin signaling, liver morphogenesis, organ laterality, lateral plate mesoderm, epithelial-mesenchymal interactions, cell repulsion, cell protrusions, cell polarity
- MeSH terms
- Animals, Cell Movement, Epithelium, Functional Laterality, Liver, Mesoderm, Morphogenesis, Pseudopodia, Zebrafish, Body Patterning, Zebrafish Proteins, Receptors, Eph Family, Ephrin-B1, Ephrin-B3, Cell Shape
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