Mesoderm formation in response to Brachyury requires FGF signalling

Area of Science:

• Developmental Biology
• Molecular Genetics

Background:

• The Brachyury (T) gene is crucial for posterior mesoderm formation and axial development in vertebrates.
• Xenopus homologue of Brachyury, Xbra, is induced by FGF and activin, and its ectopic expression triggers mesoderm formation.
• Brachyury proteins are sequence-specific DNA-binding proteins likely regulating downstream genes.

Purpose of the Study:

• To investigate the regulatory relationship between Xbra and fibroblast growth factor (FGF) signaling in Xenopus development.
• To elucidate the role of FGF signaling in mediating Brachyury's mesoderm-inducing activity.

Main Methods:

• Expression of dominant-negative FGF receptor in Xenopus embryos to inhibit Xbra's mesoderm-inducing activity.
• Analysis of gene expression changes upon ectopic Xbra expression and FGF treatment.
• Cell dissociation experiments to assess Xbra expression stability.

Main Results:

• A dominant-negative FGF receptor blocked Xbra's mesoderm-inducing capacity.
• Ectopic Xbra expression induced embryonic FGF gene transcription, and FGF subsequently induced Xbra expression, indicating a feedback loop.
• Disruption of cell-cell contact in Xbra-expressing cells led to rapid Xbra downregulation, which was rescued by FGF addition.

Conclusions:

• Mesoderm formation in Xenopus necessitates an intact FGF signaling pathway downstream of Brachyury.
• A regulatory loop exists where Brachyury activates FGF expression, and FGF, in turn, maintains Brachyury expression.
• This feedback mechanism is critical for sustained mesoderm development and axial patterning.