A note on the importance of fibroblast growth factors in the development of embryos.

1. SYED MUHAMMAD KHAN (BS HONS. ZOOLOGY)
pg. 1
Fibroblast Growth Factors
The fibroblast growth factor (FGF) is a family of paracrine factors (growth factors) that
comprises nearly two dozen structurally related members. The FGF genes can generate
hundreds of protein isoforms by varying their RNA splicing or initiation codons in
different tissues.
VARIOUS TYPES OF FGFs:
 Fgf1 protein / acidic FGF is important for regeneration.
 Fgf2 / basic FGF is very important in blood vessel formation.
 Fgf7 / keratinocyte growth factor is critical in skin development.
 Fgf8 is important during limb development and lens induction. Fgf8 is usually made
by the optic vesicle that contacts the outer ectoderm of the head.
Although FGFs can often substitute for one another, the expression patterns of the
FGFs and their receptors give them separate functions.
FUNCTIONS OF FGFs:
 Fibroblast growth factors (FGFs) act as mitogens (causes mitosis).
 FGF is critical during the normal development of both vertebrates and invertebrates
– any irregularities in their function leads to a range of developmental defects.
 FGFs promote endothelial cell proliferation and the physical organization of
endothelial cells into tube-like structures (hence they are important in forming new
blood vessels).
 FGFs play an important role in wound healing.
 FGFs play important roles during the development of the central nervous system.
 FGFs are also important for the maintenance of the adult brain.
 FGF proteins are also involved in paracrine signaling.

2. SYED MUHAMMAD KHAN (BS HONS. ZOOLOGY)
pg. 2
 Mechanism of FGF functions:
FGFs often work by activating a set of receptor tyrosine kinases called the fibroblast
growth factor receptors (FGFRs). When an FGFR binds an FGF (and only when it binds
an FGF), the dormant kinase (FGFR is a kinase, it is dormant but is activated when
FGF binds with it) is activated and phosphorylates certain proteins (including other
FGFRs) within the responding cell. These proteins, once activated, can perform new
functions.
 FGFs & RTK Pathway:
“The RTK pathway is a signal transduction pathway activated by fibroblast growth
factors and other paracrine factors. It is important for developmental processes.”
The steps for the RTK pathway are as follows:
1. The pathway begins at the cell surface, where an RTK binds its specific ligand.
Ligands that bind to RTKs include the fibroblast growth factors, epidermal growth
factors, platelet-derived growth factors, and stem cell factor. Each RTK can bind only
one or a small set of these ligands, and when it binds its ligand, it undergoes a
conformational change that enables it to dimerize with another RTK.
2. This conformational change activates the latent (inactive) kinase activity of each
RTK, and these receptors phosphorylate each other on particular tyrosine residues
(autophosphorylation).
3. The phosphorylated tyrosine on the receptor is then recognized by an adaptor
protein.
4. The adaptor protein serves as a bridge that links the phosphorylated RTK to a
powerful intracellular signaling system. The adaptor protein also activates a G
protein, such as Ras (through a protein called GNRP).

3. SYED MUHAMMAD KHAN (BS HONS. ZOOLOGY)
pg. 3
5. The active Ras G protein associates with a kinase called Raf. The G protein recruits
the inactive Raf protein to the cell membrane, where it becomes active.
6. The Raf protein is a kinase that activates the MEK protein by phosphorylating it.
7. MEK is itself a kinase, which activates the ERK protein by phosphorylation.
8. ERK is also a kinase that enters the nucleus and phosphorylates certain
transcription factors.
9. Transcription factors, when activated, determine the developmental course of the
cell.
Figure: RTK signal transduction pathway.