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EphrinB1/EphB3b Coordinate Bidirectional Epithelial-Mesenchymal Interactions Controlling Liver Morphogenesis and
Jordi Cayuso1, Aliaksandr Dzementsei2, Johanna C Fischer1
1Division of Developmental Biology, Mill Hill Laboratories, The Francis Crick Institute, London NW7 1AA, UK.
Bidirectional Eph/Ephrin signaling between liver cells and surrounding tissues coordinates zebrafish liver development. This crosstalk guides tissue movement, ensuring correct organ positioning and leftward liver bud formation.
Area of Science:
- Developmental Biology
- Cell Signaling
- Organogenesis
Background:
- Organ positioning requires coordinated tissue movement, but underlying mechanisms are poorly understood.
- Eph/Ephrin signaling is crucial for cell-cell communication and tissue patterning.
Purpose of the Study:
- To elucidate the molecular mechanisms coordinating hepatic endoderm and lateral plate mesoderm (LPM) movement during zebrafish liver formation.
- To investigate the role of EphrinB1 and EphB3b in mediating cell-cell interactions and asymmetric organ positioning.
Main Methods:
- Zebrafish model system
- Analysis of EphrinB1 and EphB3b signaling pathways
- Cellular imaging and migration assays
- Investigating cell-cell interactions and tissue interfaces
Main Results:
- Bidirectional EphrinB1/EphB3b signaling coordinates hepatic endoderm and LPM movement for asymmetric liver positioning.
- EphrinB1 on hepatoblasts regulates migration and LPM interaction; EphB3b on LPM controls its polarity and movement.
- Eph/Ephrin signaling mediates hepatoblast motility via cellular protrusions and long-distance contacts.
- Intracellular EphrinB1 domains promote extension formation, while EphB3b interactions destabilize them.
Conclusions:
- Bidirectional signaling between epithelial (hepatoblasts) and mesenchyme-like (LPM) tissues is essential for liver bud formation and leftward asymmetry.
- Eph/Ephrin-mediated cell repulsion and attraction orchestrate complex tissue movements during organogenesis.
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