Abstract
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. 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. 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.
Highlights
The vertebrate fibroblast growth factor (FGF) signalling network is complex
The most robust increases occurred with iFgfr1 and 2, with only a modest upregulation resulting from iFgfr4 activation
In addition to egr1, cdx1, msx2, wnt8a and spry2, which have been identified as being positively regulated by FGF signalling in previous Xenopus studies, we found both the nodal antagonist gene lefty and the nek6 kinase gene to be upregulated by iFgfr1 and iFgfr2 which represent novel targets of FGF regulation at this later stage (Supporting Information Tables 1 and 3)
Summary
The vertebrate fibroblast growth factor (FGF) signalling network is complex. The human genome encodes 22 FGF family proteins (Itoh and Ornitz, 2008; Ornitz and Itoh, 2015). FGF1-9 and 19–23 are secreted proteins, and fulfil either paracrine or endocrine functions by activating a family of four cell surface receptor tyrosine kinases (FGFR 1, 2, 3 and 4). Another subgroup of FGFs (FGF11-14) are not secreted, do not bind to FGFRs and have intracellular functions (Goldfarb, 2005; Itoh and Ornitz, 2008; Ornitz and Itoh, 2015). A wealth of previous studies has demonstrated important roles for FGF signalling in regulating gene expression during cell lineage specification in amphibian development. In this study we make use of synthetic drug inducible versions of Xenopus Fgfr and 4 (iFgfr and 4) to undertake a comparative analysis of their activities in the tissues of the developing embryo
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