Mesoderm formation in response to Brachyury requires FGF signalling.
BACKGROUND
The Brachyury (T) gene is required for the formation of posterior mesoderm and for axial development in both mouse and zebrafish embryos. In these species, and in Xenopus, the gene is expressed transiently throughout the presumptive mesoderm, and transcripts then persiste in notochord and posterior tissues. In Xenopus embryos, expression of the Xenopus homologue of Brachyury, Xbra, can be induced in presumptive ectoderm by basic fibroblast growth factor (FGF) and activin; in the absence of functional FGF or activin signalling pathways, expression of the gene is severely reduced. Ectopic expression of Xbra in presumptive ectoderm causes mesoderm to be formed. As Brachyury and its homologues encode sequence-specific DNA-binding proteins, it is likely that each functions by directly activating downstream mesoderm-specific genes.


RESULTS
We show that expression in Xenopus embryos of RNA encoding a dominant-negative FGF receptor inhibits the mesoderm-inducing activity of Xbra. We demonstrate that ectopic expression of Xbra activates transcription of the embryonic FGF gene, and that embryonic FGF can induce expression of Xbra. This suggests that the two genes are components of a regulatory loop. Consistent with this idea, dissociation of Xbra-expressing cells causes a dramatic and rapid reduction in levels of Xbra, but the reduction can be inhibited by addition of FGF.


CONCLUSIONS
Formation of mesoderm tissue requires an intact FGF signalling pathway downstream of Brachyury. This requirement is due to a regulatory loop, in which Brachyury activates expression of a member of the FGF family, and FGF maintains expression of Brachyury.(ABSTRACT TRUNCATED AT 250 WORDS)
Schulte-Merker
S
S
Laboratory of Developmental Biology, National Institute for Medical Research, London, UK.
Smith
J C
JC
D028341:Activins; D000818:Animals; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D005326:Fetal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007265:Inhibins / Q000502:physiology; D008648:Mesoderm / Q000502:physiology*; D012313:RNA / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D020825:T-Box Domain Proteins; D014158:Transcription, Genetic / Q000502:physiology; D014981:Xenopus; D000098908:Brachyury Protein
D028341:Activins; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; D005346:Fibroblast Growth Factors; D007265:Inhibins; D012313:RNA; D017468:Receptors, Fibroblast Growth Factor; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein