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FGF signaling in gastrulation and neural development in Nematostella vectensis, an anthozoan cnidarian


The fibroblast growth factor (FGF) signal transduction pathway serves as one of the key regulators of early metazoan development, displaying conserved roles in the specification of endodermal, mesodermal, and neural fates during vertebrate development. FGF signals also regulate gastrulation, in part, by triggering epithelial to mesenchymal transitions in embryos of both vertebrates and invertebrates. Thus, FGF signals coordinate gastrulation movements across many different phyla. To help understand the breadth of FGF signaling deployment across the animal kingdom, we have examined the presence and expression of genes encoding FGF pathway components in the anthozoan cnidarian Nematostella vectensis. We isolated three FGF ligands (NvFGF8A, NvFGF8B, and NvFGF1A), two FGF receptors (NvFGFRa and NvFGFRb), and two orthologs of vertebrate FGF responsive genes, Sprouty (NvSprouty), an inhibitor of FGF signaling, and Churchill (NvChurchill), a Zn finger transcription factor. We found these FGF ligands, receptors, and response gene expressed asymmetrically along the oral/aboral axis during gastrulation and in a developing chemosensory structure of planula stages known as the apical tuft. These results suggest a conserved role for FGF signaling molecules in coordinating both gastrulation and neural induction that predates the Cambrian explosion and the origins of the Bilateria.

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Correspondence to Mark Q. Martindale.

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Communicated by D. A. Weisblat

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A Bayesian phylogenetic analysis of FGF ligands. Previous studies have identified eight classes of FGFs within the Metazoa (Popovici et al. 2005). We identified 13 putative genes that possessed FGF core domains within the N. vectensis genome (Joint Genome Institute). Of the 13, a Bayesian analysis confirms the orthology for four FGF ligands (blue arrows) all within the FGF-D class (FGF8/17/18). The remaining nine ligands (black arrows) in the N. vectensis genome appear to cluster together and may either represent cnidarian-specific FGF groups or belong to one of the established classes, but the phylogenetic relationship has been obscured. N. vectensis sequences are shown in bold with arrows. Boxes demark those FGF ligands, where expression patterns have been determined. Numbers above branches indicate posterior probabilities (GIF 20 kb)


A Bayesian phylogenetic analysis of FGFRs. N. vectensis possesses 3 putative RTKs that by BLASTX searches were classified as FGFRs. A Bayesian phylogenetic analysis confirms that two of the three are legitimate FGFRs. NvFGFRa and NvFGFRb are most closely related to an FGFR from a hydrozoan cnidarian, Hydra FGFR-like (kringelchen) and the lone FGFR in the C. elegans genome, egl-15. The third receptor, NvFGFRc, groups with a hydrozoan RTK of a different family (P. carnea VEGFR) and is likely not a true FGFR. N. vectensis FGFRs are indicated by boxes and arrows. Numbers above branches indicate posterior probabilities (GIF 13 kb)


A Bayesian phylogenetic analysis of sprouty related metazoan genes. The N. vectensis genome only contained one potential sprouty/spred family member. Bayesian analysis shows that the NvSprouty ortholog forms a sister group to vertebrate and Drosophila sprouty genes, to the exclusion of Spred genes, suggesting that NvSprouty is a definitive sprouty ortholog. The N. vectensis sprouty ortholog is indicated by a box and an arrow. Numbers above branches indicate posterior probabilities (GIF 9 kb)


Bayesian phylogenetic analysis of metazoan Churchill (ChCh) genes, a zinc finger transcription factor. The N. vectensis genome only contained one potential ortholog of Churchill, which forms a sister group relationship with the echinoderm, S. purpuratus Churchill gene with 100% posterior probability. N. vectensis NvChurchill gene is indicated by a box and an arrow. Numbers above branches indicate posterior probabilities (GIF 6 kb)


NvFGF8B is expressed exclusively at the aboral end during development. Transcripts for NvFGF8B were not detectable during cleavage stages (data not shown) and throughout gastrulation (a). During planula (b) and polyp (c) stages, transcripts were detectable in a few endodermal cells at the aboral end, below the apical tuft. All embryo views are lateral with the asterisk denoting the site of gastrulation and future mouth (GIF 92 kb)


A complete receptor tyrosine kinase signaling pathway exists in Cnidaria. Besides FGF pathway ligands, receptors, and target genes, cnidarians also appear to possess orthologs to the canonical FGF RTK signal transduction pathway that is conserved throughout Bilateria. Distal to FGFRs, this pathway in vertebrates consists of FRS2, Grb2, SOS, Ras, Raf, MEK, and ERK, operating sequentially to relay intracellular signals from cell surface to nuclear target genes (Eswarakumar et al. 2005). Upon receptor activation, FRS2, an adaptor protein, binds the FGFR phosphorylated cytoplasmic tails and recruits Grb2, also an adaptor protein. Grb2 recruits SOS, a guanine nucleotide exchange factor that binds and activates the small GTPase, Ras. Activated Ras binds Raf, a MAP kinase kinase kinase that phosphorylates and activates MEK, a MAP kinase kinase. MEK subsequently activates Erk, a MAP kinase that phosphorylates and regulates nuclear transcription factors (ETS) and their regulators to affect gene activity. Potential orthologs for nearly all of these components, with the exception of FRS2, were identified by BLAST searches of the assembly of the N. vectensis genome (Joint Genome Institute). The existence of this conserved pathway in N. vectensis provides further evidence that FGF/RTK signaling is an ancient, conserved pathway (GIF 7 kb)

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Nexus file for FGF ligand phylogenetic analysis (DOC 82 kb)


Nexus file for FGFR phylogenetic analysis (DOC 47 kb)


Nexus file for Sprouty phylogenetic analysis (DOC 27 kb)


Nexus file for Churchill phylogenetic analysis (DOC 22 kb)

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Matus, D.Q., Thomsen, G.H. & Martindale, M.Q. FGF signaling in gastrulation and neural development in Nematostella vectensis, an anthozoan cnidarian. Dev Genes Evol 217, 137–148 (2007). https://doi.org/10.1007/s00427-006-0122-3

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  • Gastrulation
  • Neurogenesis
  • Evolution of development