Fibroblast Growth Factors: from Molecular Evolution to Roles in Development, Metabolism and Disease

Overview

Journal J Biochem

Publisher Oxford University Press

Specialty Biochemistry

Date 2010 Oct 14

PMID 20940169

Citations 333

Authors

Nobuyuki Itoh

David M Ornitz

Affiliations

Soon will be listed here.

Abstract

Fibroblast growth factors (FGFs) are a family of structurally related polypeptides that are essential for embryonic development and that function postnatally as homoeostatic factors, in the response to injury, in the regulation of electrical excitability of cells and as hormones that regulate metabolism. In humans, FGF signalling is involved in developmental, neoplastic, metabolic and neurological diseases. Fgfs have been identified in metazoans but not in unicellular organisms. In vertebrates, FGFs can be classified as having intracrine, paracrine and endocrine functions. Paracrine and endocrine FGFs act via cell-surface FGF receptors (FGFRs); while, intracrine FGFs act independent of FGFRs. The evolutionary history of the Fgf family indicates that an intracrine Fgf is the likely ancestor of the Fgf family. During metazoan evolution, the Fgf family expanded in two phases, after the separation of protostomes and deuterostomes and in the evolution of early vertebrates. These expansions enabled FGFs to acquire diverse actions and functions.

Citing Articles

Molecular roles in membrane receptor signaling pathways and cascade reactions in chondrocytes: a review.

Zhu Y, Zhu J, Wang X, Wang P, Liu R J Mol Histol. 2025; 56(2):94.

PMID: 39988650 DOI: 10.1007/s10735-025-10368-9.

FGF-based drug discovery: advances and challenges.

Chen G, Chen L, Li X, Mohammadi M Nat Rev Drug Discov. 2025; .

PMID: 39875570 DOI: 10.1038/s41573-024-01125-w.

FGF21 ameliorates diabetic nephropathy through CDK1-dependently regulating the cell cycle.

Zhang Y, Wang F, Zhang C, Yao F, Zhang B, Zhang Y Front Pharmacol. 2025; 15():1500458.

PMID: 39830349 PMC: 11739279. DOI: 10.3389/fphar.2024.1500458.

The Complexity and Significance of Fibroblast Growth Factor (FGF) Signaling for FGF-Targeted Cancer Therapies.

Nguyen A, Facey C, Boman B Cancers (Basel). 2025; 17(1.

PMID: 39796710 PMC: 11720651. DOI: 10.3390/cancers17010082.

Comprehensive analysis of scRNA-seq and bulk RNA-seq reveals the non-cardiomyocytes heterogeneity and novel cell populations in dilated cardiomyopathy.

He S, Li C, Lu M, Lin F, Hu S, Zhang J J Transl Med. 2025; 23(1):17.

PMID: 39762897 PMC: 11702085. DOI: 10.1186/s12967-024-05983-1.

References

Guo L, Degenstein L, Fuchs E . Keratinocyte growth factor is required for hair development but not for wound healing. Genes Dev. 1996; 10(2):165-75. DOI: 10.1101/gad.10.2.165. View

Itoh N . The Fgf families in humans, mice, and zebrafish: their evolutional processes and roles in development, metabolism, and disease. Biol Pharm Bull. 2007; 30(10):1819-25. DOI: 10.1248/bpb.30.1819. View

Ohuchi H, Hori Y, Yamasaki M, Harada H, Sekine K, Kato S . FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development. Biochem Biophys Res Commun. 2000; 277(3):643-9. DOI: 10.1006/bbrc.2000.3721. View

Harada M, Murakami H, Okawa A, Okimoto N, Hiraoka S, Nakahara T . FGF9 monomer-dimer equilibrium regulates extracellular matrix affinity and tissue diffusion. Nat Genet. 2009; 41(3):289-98. PMC: 2676118. DOI: 10.1038/ng.316. View

Gao X, Scott W, Wang G, Mayhew G, Li Y, Vance J . Gene-gene interaction between FGF20 and MAOB in Parkinson disease. Ann Hum Genet. 2008; 72(Pt 2):157-62. DOI: 10.1111/j.1469-1809.2007.00418.x. View

Brusse E, de Koning I, Maat-Kievit A, Oostra B, Heutink P, Van Swieten J . Spinocerebellar ataxia associated with a mutation in the fibroblast growth factor 14 gene (SCA27): A new phenotype. Mov Disord. 2005; 21(3):396-401. DOI: 10.1002/mds.20708. View

Feldman B, Poueymirou W, Papaioannou V, DeChiara T, Goldfarb M . Requirement of FGF-4 for postimplantation mouse development. Science. 1995; 267(5195):246-9. DOI: 10.1126/science.7809630. View

Alvarez Y, Alonso M, Vendrell V, Zelarayan L, Chamero P, Theil T . Requirements for FGF3 and FGF10 during inner ear formation. Development. 2003; 130(25):6329-38. DOI: 10.1242/dev.00881. View

Rohmann E, Brunner H, Kayserili H, Uyguner O, Nurnberg G, Lew E . Mutations in different components of FGF signaling in LADD syndrome. Nat Genet. 2006; 38(4):414-7. DOI: 10.1038/ng1757. View

10.

Xiao M, Xu L, Laezza F, Yamada K, Feng S, Ornitz D . Impaired hippocampal synaptic transmission and plasticity in mice lacking fibroblast growth factor 14. Mol Cell Neurosci. 2007; 34(3):366-77. DOI: 10.1016/j.mcn.2006.11.020. View

11.

Zhang X, Ibrahimi O, Olsen S, Umemori H, Mohammadi M, Ornitz D . Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem. 2006; 281(23):15694-700. PMC: 2080618. DOI: 10.1074/jbc.M601252200. View

12.

Schreuder T, Marsman H, Lenicek M, van Werven J, Nederveen A, Jansen P . The hepatic response to FGF19 is impaired in patients with nonalcoholic fatty liver disease and insulin resistance. Am J Physiol Gastrointest Liver Physiol. 2010; 298(3):G440-5. DOI: 10.1152/ajpgi.00322.2009. View

13.

durovcova V, Marek J, Hana V, Matoulek M, Zikan V, Haluzikova D . Plasma concentrations of fibroblast growth factors 21 and 19 in patients with Cushing's syndrome. Physiol Res. 2009; 59(3):415-422. DOI: 10.33549/physiolres.931801. View

14.

Itoh N, Ornitz D . Evolution of the Fgf and Fgfr gene families. Trends Genet. 2004; 20(11):563-9. DOI: 10.1016/j.tig.2004.08.007. View

15.

Sun X, Meyers E, Lewandoski M, Martin G . Targeted disruption of Fgf8 causes failure of cell migration in the gastrulating mouse embryo. Genes Dev. 1999; 13(14):1834-46. PMC: 316887. DOI: 10.1101/gad.13.14.1834. View

16.

Kurosu H, Choi M, Ogawa Y, Dickson A, Goetz R, Eliseenkova A . Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J Biol Chem. 2007; 282(37):26687-26695. PMC: 2496965. DOI: 10.1074/jbc.M704165200. View

17.

Shakkottai V, Xiao M, Xu L, Wong M, Nerbonne J, Ornitz D . FGF14 regulates the intrinsic excitability of cerebellar Purkinje neurons. Neurobiol Dis. 2008; 33(1):81-8. PMC: 2652849. DOI: 10.1016/j.nbd.2008.09.019. View

18.

Xu J, Liu Z, Ornitz D . Temporal and spatial gradients of Fgf8 and Fgf17 regulate proliferation and differentiation of midline cerebellar structures. Development. 2000; 127(9):1833-43. DOI: 10.1242/dev.127.9.1833. View

19.

Dover K, Solinas S, DAngelo E, Goldfarb M . Long-term inactivation particle for voltage-gated sodium channels. J Physiol. 2010; 588(Pt 19):3695-711. PMC: 2998221. DOI: 10.1113/jphysiol.2010.192559. View

20.

Vincentz J, McWhirter J, Murre C, Baldini A, Furuta Y . Fgf15 is required for proper morphogenesis of the mouse cardiac outflow tract. Genesis. 2005; 41(4):192-201. DOI: 10.1002/gene.20114. View