Fibroblast Growth Factors: Evolution

David M Ornitz, Washington University School of Medicine, St. Louis, Missouri, USA

Published online: December 2007

DOI: 10.1002/9780470015902.a0006134.pub2

Fibroblast growth factors (FGFs) and their receptors (FGF receptors) constitute a signalling system conserved throughout animal evolution. Most members of the FGF family signal across adjacent tissue boundaries and are essential for a variety of developmental and physiological processes. One subfamily of vertebrate FGFs, that may have originated in primitive chordates, appears to have evolved novel functions within neurons. Another subfamily of FGFs has acquired hormone-like properties, regulating physiological processes in the adult.

Keywords: fibroblast growth factor (FGF); FGF receptor tyrosine kinase (FGFR); endocrine hormone; heparin/heparan sulfate; neurophysiology; klotho

Figure 1. Phylogenetic tree for the human FGF gene family. Branch lengths (bootstrap values) are proportional to the distances between the taxa. Seven related subfamilies of Fgfs have been identified. Adapted from Kim (2001).
Figure 2. Structural features of the FGF polypeptide. The N-terminus of many of the FGFs (3–8, 10, 15, 17–19, 21–23) contain a signal sequence (shaded). The N-terminus is also subject to alternative splicing in some FGFs (8, 11–14, 17, 18). The N and C-termini are variable in length. All FGFs contain a core region ‘FGF domain’ which contains conserved amino acid residues that define the FGF family. Amino acid residues present in at least 70% of all human FGFs define the core domain. Highlighted residues are identical or highly conserved among all FGFs. Spaces indicate the maximum number of intervening residues between conserved residues. N-terminus, pink; FGF domain, blue and C-terminus, purple.
Figure 3. Structural features of the FGF receptor. (a) Short form of the FGF receptor expressing immunoglobulin-like domains II and III. The shaded region in immunoglobulin-like domain III is subject to alternative splicing. (b) and (c) Full-length FGF receptor including immunoglobulin-like domain I (green), II and III. (b) The immunoglobulin-like domain IIIb splice form (pink) of the FGF receptor is expressed predominantly in epithelial tissues. (c) The immunoglobulin-like domain IIIc splice form (blue) of the FGF receptor is expressed predominantly in mesenchymal tissues. (d) Genomic representation of alternative splicing events in FGF receptors. Immunoglobulin-like domain III is encoded by a common exon a, and by alternatively spliced exons b and c. SP, signal peptide; orange box, heparin/heparan sulfate-binding domain; I, II and III, immunoglobulin-like domains; S–S, conserved disulphide bonds in the immunoglobulin-like domains; TM, transmembrane domain; TK, tyrosine kinase domain.
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 Further Reading
    Birnbaum D, Popovici C and Roubin R (2005) A pair as a minimum: the two fibroblast growth factors of the nematode Caenorhabditis elegans. Developmental Dynamics 232: 247–255.
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    Ornitz DM (2005) FGF signaling in the developing endochondral skeleton. Cytokine Growth Factor Reviews 16: 205–213.
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Related Sub-Topics:

Molecular Evolution | Protein Evolution | Evolution of Coding and Functional Modules
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Article Title: Fibroblast Growth Factors: Evolution
 
How to Cite close
Ornitz, David M(Dec 2007) Fibroblast Growth Factors: Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006134.pub2]