A comparative analysis of fibroblast growth factor receptor signalling during Xenopus development. (17th February 2020)

• Record Type: Journal Article
• Authors: Brunsdon, Hannah; Isaacs, Harry V.
• Is Part Of: Biology of the cell. Volume 112:Number 5(2020)
• Page Start: 127
• Page End: 139
• Publication Date: 2020-02-17
• Subjects: cellular differentiation -- development -- growth factors; Cytology -- Periodicals; Electron microscopy -- Periodicals; 571.6
• DOI: 10.1111/boc.201900089
• Languages: English
• ISSNs: 0248-4900

Abstract

Abstract : Background Information: The fibroblast growth factor (FGF) signalling system of vertebrates is complex. In common with other vertebrates, secreted FGF ligands of the amphibian Xenopus signal through a family of four FGF receptor tyrosine kinases (fgfr1, 2, 3 and 4). A wealth of previous studies has demonstrated important roles for FGF signalling in regulating gene expression during cell lineage specification in amphibian development. In particular, FGFs have well‐established roles in regulating mesoderm formation, neural induction and patterning of the anteroposterior axis. However, relatively little is known regarding the role of individual FGFRs in regulating FGF‐dependent processes in amphibian development. In this study we make use of synthetic drug inducible versions of Xenopus Fgfr1, 2 and 4 (iFgfr1, 2 and 4) to undertake a comparative analysis of their activities in the tissues of the developing embryo. Results: We find that Xenopus Fgfr1 and 2 have very similar activities. Both Fgfr1 and Fgfr2 are potent activators of MAP kinase ERK signalling, and when activated in the embryo during gastrula stages regulate similar cohorts of transcriptional targets. In contrast, Fgfr4 signalling in naïve ectoderm and neuralised ectoderm activates ERK signalling only weakly compared to Fgfr1/2. Furthermore, our analyses indicate that in Xenopus neural tissue the Fgfr4 regulated transcriptome is very different from that of Fgfr1. Conclusion and significance: We conclude that signalling downstream of Fgfr1 and 2 regulates similar processes in amphibian development. Interestingly, many of the previously identified canonical transcriptional targets of FGF regulation associated with germ layer specification and patterning are regulated by Fgfr1/Fgfr2 signalling. In contrast, the downstream consequences of Fgfr4 signalling are different, although roles for Fgfr4 signalling in lineage specification and anteroposterior patterning are also indicated. Abstract : Research article : Fgf signalling is important in many developmental processes, but the contribution of individual Fgf receptors (Fgfrs) is unclear. We used inducible Fgf receptors (iFgfrs) to investigate the effects of iFgfr1, 2 and 4 activation during Xenopus neural development. Although iFgfr1 and 2 behaved similarly, iFgfr4 had distinct effects on MAPK signalling pathway activity, gene expression and embryo morphology. This suggests that as well as receptor–ligand interactions, Fgfrs themselves are an important point of control for Fgf signalling output during development.