Fibroblast Growth Factor (FGF) were originally identified by their ability to stimulate fibroblast cell proliferation but have a role in a growing number of different tissues development and differentiation and continue to have a role in the adult.
The first two identified factors were originally given the nomenclature of acidic or basic. We now know there to be at least 17 different FGFs. These protein growth factors are bound by 4 different cell membrane receptors (FGFR1-4). FGFRs belong to the tyrosine kinase receptor family.
The mammalian Fgf family can be divided into the intracellular Fgf11/12/13/14 subfamily (iFGFs), the endocrine hormone-like Fgf15/21/23 subfamily (hFGFs), and the paracrine canonical Fgf subfamilies, including Fgf1/2/5, Fgf3/4/6, Fgf7/10/22, Fgf8/17/18, and Fgf9/16/20.
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Itoh N, Ornitz DM. Functional evolutionary history of the mouse Fgf gene family. Dev Dyn. 2008 Jan;237(1):18-27.
"Canonical FGFs function in a paracrine manner, while hFGFs function in an endocrine manner. We conclude that the ancestral Fgfs for these subfamilies acquired this functional diversity before the evolution of vertebrates. During the evolution of early vertebrates, the Fgf subfamilies further expanded to contain three or four members in each subfamily.."
FGF Receptor
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Itoh N, Ornitz DM. Functional evolutionary history of the mouse Fgf gene family. Dev Dyn. 2008 Jan;237(1):18-27.
Xu X, et al. [See Related Articles] Fibroblast growth factor receptors (FGFRs) and their roles in limb development. Cell Tissue Res. 1999 Apr;296(1):33-43. Review. PMID: 10199963; UI: 99216336.
Signaling during development, though complex, can also be grouped into a few specific classes. These mechanisms have also been listed and described briefly on Signaling Mechanisms Introduction page.
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Developmental Dynamics
Journal of Neurobiology
Molecular Biology of the Cell (4th Edn) Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York: Garland Publishing; 2002.
Developmental Biology (6th Edn) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000.
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antisense- a sequence of DNA that is complementary usually to coding sequence of DNA or mRNA. Has been used experimentally to perturb or block gene expression. Also a mechanism that has been found to occur naturally as a regulatory mechanism.
autosomal inheritance- some hereditary diseases are described as autosomal which means that the disease is due to a DNA error in one of the 22 pairs that are not sex chromosomes. Both boys and girls can then inherit this error. If the error is in a sex chromosome, the inheritance is said to be sex-linked.
base- another term for nucleotide (usually a t c g).
base pair- Double stranded DNA has nucleotides A-T, C-G, paired by hydrogen bonds (2 for AT, 3 for GC). Note this means that GC is harder to separate that AT.
DNA- DeoxyriboNucleic Acid. The genetic material found in mammalian chromosomes and mitochondria. Consisting of 4 nucleic acids (ATCG) that combine in a triptych (3 nucleotide) code for protein amino acids (3nt=1aa).
DNA duplex- double stranded base-paired DNA forming a helix.
dominant inheritance-With autosomal dominant inheritance, there is an error in one of the 22 chromosome pairs. But the damaged gene dominates over the normal gene received from the other parent. If one of the parents has a disease caused by an autosomal dominant gene, all the children will have a 50 per cent risk of inheriting the dominant gene and a 50 per cent chance of not inheriting it. The children who do not inherit the damaged dominant gene will not themselves suffer from the disease, nor will they be able to pass the gene on to future children. This type of inheritance is present for example in Huntington's disease.
exon- a block of protein encoding sequence of DNA in a gene. Many proteins are made of several exons "stitched" or spliced together by editing out non-coding (intron) sequences.
fasta- a format for listing DNA sequence, where the first line has descritive information followed on the next line by the sequence without numbering.
GC repeat- a string of GC sequence repeated several times. Also associated with GC expansion, a mutational process that may lead eventually to serious gene expression effects.
gene- a sequence of DNA that encodes an individual protein.
genetic code- the 3 nucleotide sequence that forms a codon for a single amino acid or stop. See the gene code.
genome- the complete genetic information in the form of DNA available to a specific species.
hairpin loop- a folding of RNA generated by base pairing making a "===()" structure, the end loop and or stem of this structure can then interact with proteins or other RNA.
intron- a block of DNA within a gene not encoding a protein. Edited, spliced, out during transcription into mRNA. Originally thought not to contain any information, but more and more this appears not to be the case. Some intron sequences have been shown to regulate gene expression during development (eg c elegans, Lin 14)
mRNA- messenger, transcribed from DNA in the nucleus and in mitochondria. Is translated by the ribosome in the cytoplasm (or mitochondrial matrix). Intermediate step in gene expression. (DNA-> mRNA-> protein).
mutation- any process which results in the alteration of the DNA sequence. Some conservative mutations may have no effect on the final amino acid encoded.
point mutation- a change in a single nucleotide.
recessive inheritance-With autosomal recessive inheritance, the diseased individual has inherited the same gene damage from both father and mother. The damage is found on both chromosomes in the pair. But as this is not ´dominant gene damageª, neither father nor mother show any sign of disease, they are healthy carriers of the gene. We are all carriers of about five recessive genes of this type, but as spouses are seldom carriers of exactly the same damaged gene(s), all will probably go well in the next generation.
ribosome- complex of rRNA and ribosomal proteins, bind mRNA and translate it into protein.
RNA- RiboNucleic Acid. The intermediate nucleic acid involved in gene expression. It comes in 3 forms: tRNA, mRNA, rRNA.
rRNA- ribosomal, translates mRNA into protein. rRNA provides the "scaffolding" on which many ribosomal proteins are assembled as 2 subunits that themselves assemble to form a ribosome. rRNA genes are localized to the nucleolus in the nucleus, a sometimes visible region of DNA usually constantly being transcribed.
telomere- regions at the end of chromosomes. Shortening of the telomeres is thought to be associated with cellular aging. The enzyme that maintains the telomere is called telomerase. Introducing this gene into a cell can extend the cells lifespan.
transcription factor- a protein which binds to DNA activating (usually) gene expression. There are many different ways and forms that this activation can take place, but most transcription factors fall into specific classes (eg zinc fingers, helix loop helix).
tRNA- transfer, binds single amino acids acts as a "donor' for protein synthesis.
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This section of notes introduces the topic of fibroblast growth factor proteins (FGF) which is a family of growth facotrs with many different functions.
Molecular mechanisms of development is an exciting area and requires a variety of different skills. This page introduces only a few examples and should give you a feel for the topic.
Please email Dr Mark Hill if you wish to make a comment about this current project.
Variation