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Involvement of NF-kappaB associated proteins in FGF-mediated mesoderm induction
C W Beck1, D J Sutherland, H R Woodland
1Department of Biological Sciences, University of Warwick, Coventry, United Kingdom. bsscb@bath.ac.uk
The International Journal of Developmental Biology
|March 13, 1998
Summary
Mutant XrelA deltaSP inhibits mesoderm induction by blocking embryonic FGF signaling downstream of MAP kinase, impacting cell movements but not dorsal differentiation in Xenopus embryos.
Area of Science:
- Developmental Biology
- Molecular Biology
- Cell Signaling
Background:
- NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a key transcription factor regulating immune responses and development.
- XrelA is a Xenopus homolog of the RelA (p65) subunit of NF-kappaB.
- Fibroblast Growth Factor (FGF) signaling plays a critical role in embryonic development, including mesoderm induction and cell movements.
Purpose of the Study:
- To investigate the role of XrelA in mesoderm induction in Xenopus embryos.
- To characterize the function of XrelA deltaSP, a dominant-negative mutant of XrelA, in FGF signaling pathways.
- To determine the specific stage and downstream targets of XrelA's involvement in FGF-mediated developmental processes.
Main Methods:
- mRNA injection of XrelA deltaSP and NF-kappaB1 (p50) mutants into Xenopus oocytes and embryos.
- Assessment of DNA binding and transactivation of kappaB-dependent promoters.
- Analysis of mesoderm induction in animal cap explants.
- Evaluation of elongation movements and dorsal cytodifferentiation.
- Investigation of FGF signaling pathway components, including MAP kinase and Xbra expression.
Main Results:
- XrelA deltaSP and a mammalian NF-kappaB1 (p50) derivative exhibited dominant inhibitory activity, suppressing DNA binding of rel family members and transactivation.
- Expression of XrelA deltaSP blocked mesoderm induction by bFGF (basic FGF) and prevented activin-induced elongation movements.
- XrelA deltaSP specifically inhibited FGF signaling downstream of MAP kinase and affected the maintenance of Xbra expression by embryonic FGF (eFGF).
- The mutant primarily affected gastrula stage FGF signaling, not blastula stage maternal signaling, and impacted cell movements more than dorsal differentiation.
Conclusions:
- Zygotic FGF signaling mediated by XrelA is crucial for cell movements during Xenopus gastrulation.
- XrelA deltaSP acts as a specific inhibitor of gastrula-stage FGF signaling, downstream of MAP kinase.
- The findings suggest a distinct role for zygotic FGF action in cell migration and tissue morphogenesis compared to dorsal patterning.
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