FGF4

Last updated
FGF4
Protein FGF4 PDB 1ijt.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases FGF4 , HBGF-4, HST, HST-1, HSTF1, K-FGF, KFGF, fibroblast growth factor 4, HSTF-1, FGF-4
External IDs OMIM: 164980 MGI: 95518 HomoloGene: 1522 GeneCards: FGF4
Orthologs
SpeciesHumanMouse
Entrez

2249

14175

Ensembl

ENSG00000075388

ENSMUSG00000050917

UniProt

P08620

P11403

RefSeq (mRNA)

NM_002007

NM_010202

RefSeq (protein)

NP_001998

NP_034332

Location (UCSC) Chr 11: 69.77 – 69.78 Mb Chr 7: 144.4 – 144.42 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Fibroblast growth factor 4 is a protein that in humans is encoded by the FGF4 gene. [5] [6]

Contents

The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This gene was identified by its oncogenic transforming activity. This gene and FGF3, another oncogenic growth factor, are located closely on chromosome 11. Co-amplification of both genes was found in various kinds of human tumors. Studies on the mouse homolog suggested a function in bone morphogenesis and limb development through the sonic hedgehog (SHH) signaling pathway. [6]

Function

During embryonic development, the 21-kD protein FGF4 functions as a signaling molecule that is involved in many important processes. [7] [8] Studies using Fgf4 gene knockout mice showed developmental defects in embryos both in vivo and in vitro, revealing that FGF4 facilitates the survival and growth of the inner cell mass during the postimplantation phase of development by acting as an autocrine or paracrine ligand. [7] FGFs produced in the apical ectodermal ridge (AER) are critical for the proper forelimb and hindlimb outgrowth. [9] FGF signaling in the AER is involved in regulating limb digit number and cell death in the interdigital mesenchyme. [10] When FGF signaling dynamics and regulatory processes are altered, postaxial polydactyly and cutaneous syndactyly, two phenotypic abnormalities collectively known as polysyndactyly, can occur in the limbs. Polysyndactyly is observed when an excess of Fgf4 is expressed in limb buds of wild-type mice. In mutant limb buds that do not express Fgf8, the expression of Fgf4 still results in polysyndactyly, but Fgf4 is also able to rescue all skeletal defects that arise from the lack of Fgf8. Therefore, the Fgf4 gene compensates for the loss of the Fgf8 gene, revealing that FGF4 and FGF8 perform similar functions in limb skeleton patterning and limb development. [10] Studies of zebrafish Fgf4 knockdown embryos demonstrated that when Fgf4 signaling is inhibited, randomized left-right patterning of the liver, pancreas, and heart takes place, showing that Fgf4 is a crucial gene involved in developing left-right patterning of visceral organs. Furthermore, unlike the role of FGF4 in limb development, FGF4 and FGF8 have distinct roles and function independently in the process of visceral organ left-right patterning. [11] Fgf signaling pathway has also been demonstrated to drive hindgut identity during gastrointestinal development, and the up regulation of the Fgf4 in pluripotent stem cell has been used to direct their differentiation for the generation of intestinal Organoids and tissues in vitro. [12]

FGF4 Retrogenes

In canines the FGF4 retrogene insertion on chromosome 18 is involved in the short leg phenotype. [13] This is still a member of the FGF4 gene family. Fibroblast Growth Factor 4 is a protein coding gene, meaning it's a structural protein molecule. [14] The biological role that FGF4-18 plays is important in embryological development, specifically appropriate growth. In canines, the developmental structure this retrogene mutation patterning leads to is shortened legs due to the defects in endochondral ossification.These mutations and FGF signaling abnormalities are also linked in humans with dwarfism by preventing bones from growing to the normal length. [13] [15] This FGF4 retrogene on not only chromosome 18 but also 12 leads to shortened limbs and abnormal vertebrae associated with intervertebral disc disease. Research done at University of California-Davis has found that FGF4 retrogene on chromosome 12 is also attributed to the short legs and abnormal intervertebral disc that degenerate. [13] This particular FGF4-12 retrogene in canines leads to the short limb phenotype from dysplastic shortened long bones, premature degeneration, and calcification of the intervertebral disc; which gives a susceptibility to IVDD (intervertebral disc disease). [13] [15]

Related Research Articles

<span class="mw-page-title-main">Basic fibroblast growth factor</span> Growth factor and signaling protein otherwise known as FGF2

Fibroblast growth factor 2, also known as basic fibroblast growth factor (bFGF) and FGF-β, is a growth factor and signaling protein encoded by the FGF2 gene. It binds to and exerts effects via specific fibroblast growth factor receptor (FGFR) proteins, themselves a family of closely related molecules. Fibroblast growth factor protein was first purified in 1975; soon thereafter three variants were isolated: 'basic FGF' (FGF2); Heparin-binding growth factor-2; and Endothelial cell growth factor-2. Gene sequencing revealed that this group is the same FGF2 protein and is a member of a family of FGF proteins.

Fibroblast growth factors (FGF) are a family of cell signalling proteins produced by macrophages; they are involved in a wide variety of processes, most notably as crucial elements for normal development in animal cells. Any irregularities in their function lead to a range of developmental defects. These growth factors typically act as systemic or locally circulating molecules of extracellular origin that activate cell surface receptors. A defining property of FGFs is that they bind to heparin and to heparan sulfate. Thus, some are sequestered in the extracellular matrix of tissues that contains heparan sulfate proteoglycans and are released locally upon injury or tissue remodeling.

<span class="mw-page-title-main">FGF1</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor 1, (FGF-1) also known as acidic fibroblast growth factor (aFGF), is a growth factor and signaling protein encoded by the FGF1 gene. It is synthesized as a 155 amino acid polypeptide, whose mature form is a non-glycosylated 17-18 kDa protein. Fibroblast growth factor protein was first purified in 1975, but soon afterwards others using different conditions isolated acidic FGF, Heparin-binding growth factor-1, and Endothelial cell growth factor-1. Gene sequencing revealed that this group was actually the same growth factor and that FGF1 was a member of a family of FGF proteins.

<span class="mw-page-title-main">FGF3</span> Protein-coding gene in humans

INT-2 proto-oncogene protein also known as FGF-3 is a protein that in humans is encoded by the FGF3 gene.

<span class="mw-page-title-main">Receptor tyrosine kinase</span> Class of enzymes

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. Of the 90 unique tyrosine kinase genes identified in the human genome, 58 encode receptor tyrosine kinase proteins. Receptor tyrosine kinases have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Mutations in receptor tyrosine kinases lead to activation of a series of signalling cascades which have numerous effects on protein expression. Receptor tyrosine kinases are part of the larger family of protein tyrosine kinases, encompassing the receptor tyrosine kinase proteins which contain a transmembrane domain, as well as the non-receptor tyrosine kinases which do not possess transmembrane domains.

<span class="mw-page-title-main">Apical ectodermal ridge</span>

The apical ectodermal ridge (AER) is a structure that forms from the ectodermal cells at the distal end of each limb bud and acts as a major signaling center to ensure proper development of a limb. After the limb bud induces AER formation, the AER and limb mesenchyme—including the zone of polarizing activity (ZPA)—continue to communicate with each other to direct further limb development.

The limb bud is a structure formed early in vertebrate limb development. As a result of interactions between the ectoderm and underlying mesoderm, formation occurs roughly around the fourth week of development. In the development of the human embryo the upper limb bud appears in the third week and the lower limb bud appears four days later.

<span class="mw-page-title-main">Fibroblast growth factor receptor 1</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor receptor 1 (FGFR1), also known as basic fibroblast growth factor receptor 1, fms-related tyrosine kinase-2 / Pfeiffer syndrome, and CD331, is a receptor tyrosine kinase whose ligands are specific members of the fibroblast growth factor family. FGFR1 has been shown to be associated with Pfeiffer syndrome, and clonal eosinophilias.

<span class="mw-page-title-main">FGF7</span> Protein-coding gene in the species Homo sapiens

Keratinocyte growth factor is a protein that in humans is encoded by the FGF7 gene.

<span class="mw-page-title-main">FGF10</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor 10 is a protein that in humans is encoded by the FGF10 gene.

<span class="mw-page-title-main">Fibroblast growth factor 8</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor 8(FGF-8) is a protein that in humans is encoded by the FGF8 gene.

<span class="mw-page-title-main">FGF5</span> Mammalian protein found in Homo sapiens

Fibroblast growth factor 5 is a protein that in humans is encoded by the FGF5 gene.

<span class="mw-page-title-main">FGF18</span> Mammalian protein found in Homo sapiens

Fibroblast growth factor 18 (FGF18) is a protein that is encoded by the Fgf18 gene in humans. The protein was first discovered in 1998, when two newly-identified murine genes Fgf17 and Fgf18 were described and confirmed as being closely related by sequence homology to Fgf8. The three proteins were eventually grouped into the FGF8 subfamily, which contains several of the endocrine FGF superfamily members FGF8, FGF17, and FGF18. Subsequent studies identified FGF18's role in promoting chondrogenesis, and an apparent specific activity for the generation of the hyaline cartilage in articular joints.

<span class="mw-page-title-main">TBX2</span> Protein-coding gene in the species Homo sapiens

T-box transcription factor 2 Tbx2 is a transcription factor that is encoded by the Tbx2 gene on chromosome 17q21-22 in humans. This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. Tbx2 and Tbx3 are the only T-box transcription factors that act as transcriptional repressors rather than transcriptional activators, and are closely related in terms of development and tumorigenesis. This gene plays a significant role in embryonic and fetal development through control of gene expression, and also has implications in various cancers. Tbx2 is associated with numerous signaling pathways, BMP, TGFβ, Wnt, and FGF, which allow for patterning and proliferation during organogenesis in fetal development.

<span class="mw-page-title-main">FRS3</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor receptor substrate 3 is a protein that in humans is encoded by the FRS3 gene.

<span class="mw-page-title-main">FGF6</span> Protein-coding gene in humans

Fibroblast growth factor 6 is a protein that in humans is encoded by the FGF6 gene.

<span class="mw-page-title-main">FGF12</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor 12 is a protein that in humans is encoded by the FGF12 gene.

<span class="mw-page-title-main">FGF17</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor 17 is a protein that in humans is encoded by the FGF17 gene.

Fibroblast growth factor 20 is a protein which in humans is encoded by the FGF20 gene.

This article is about the role of Fibroblast Growth Factor Signaling in Mesoderm Formation.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000075388 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000050917 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Galland F, Stefanova M, Lafage M, Birnbaum D (Jul 1992). "Localization of the 5' end of the MCF2 oncogene to human chromosome 15q15----q23". Cytogenetics and Cell Genetics. 60 (2): 114–6. doi:10.1159/000133316. PMID   1611909.
  6. 1 2 "Entrez Gene: FGF4 fibroblast growth factor 4 (heparin secretory transforming protein 1, Kaposi sarcoma oncogene)".
  7. 1 2 Feldman B, Poueymirou W, Papaioannou VE, DeChiara TM, Goldfarb M (Jan 1995). "Requirement of FGF-4 for postimplantation mouse development". Science. 267 (5195): 246–9. Bibcode:1995Sci...267..246F. doi:10.1126/science.7809630. PMID   7809630. S2CID   31312392.
  8. ↑ Yuan H, Corbi N, Basilico C, Dailey L (Nov 1995). "Developmental-specific activity of the FGF-4 enhancer requires the synergistic action of Sox2 and Oct-3". Genes & Development. 9 (21): 2635–45. doi: 10.1101/gad.9.21.2635 . PMID   7590241.
  9. ↑ Boulet AM, Moon AM, Arenkiel BR, Capecchi MR (Sep 2004). "The roles of Fgf4 and Fgf8 in limb bud initiation and outgrowth". Developmental Biology. 273 (2): 361–72. doi:10.1016/j.ydbio.2004.06.012. PMID   15328019.
  10. 1 2 Lu P, Minowada G, Martin GR (Jan 2006). "Increasing Fgf4 expression in the mouse limb bud causes polysyndactyly and rescues the skeletal defects that result from loss of Fgf8 function". Development. 133 (1): 33–42. doi: 10.1242/dev.02172 . PMID   16308330.
  11. ↑ Yamauchi H, Miyakawa N, Miyake A, Itoh N (Aug 2009). "Fgf4 is required for left-right patterning of visceral organs in zebrafish". Developmental Biology. 332 (1): 177–85. doi:10.1016/j.ydbio.2009.05.568. PMID   19481538.
  12. ↑ Lancaster MA, Knoblich JA (2014). "Organogenesis in a dish: modeling development and disease using organoid technologies". Science. 345 (6194): 1247125. doi:10.1126/science.1247125. PMID   25035496. S2CID   16105729.
  13. 1 2 3 4 "Genetic Discovery Finds Dachshunds' Short-Leg Phenotype Linked To IVDD". www.purinaproclub.com. Retrieved 2022-04-13.
  14. ↑ "FGFR3 Gene - GeneCards | FGFR3 Protein | FGFR3 Antibody". www.genecards.org. Retrieved 2022-04-13.
  15. 1 2 Brown EA, Dickinson PJ, Mansour T, Sturges BK, Aguilar M, Young AE, Korff C, Lind J, Ettinger CL, Varon S, Pollard R (2017-10-24). "FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs". Proceedings of the National Academy of Sciences. 114 (43): 11476–11481. doi: 10.1073/pnas.1709082114 . ISSN   0027-8424. PMC   5664524 . PMID   29073074.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.