For this Growth Factor Focus week, we want to take a closer look at the FGF8 subfamily of Fibroblast Growth Factors. This subfamily comprises of FGF-8, FGF-17, and FGF-18. 

The FGF8 subfamily of the Fibroblast Growth Factors is principally involved with brain, ear, limb and eye development. The members of this family have distinct and overlapping expression patterns in various prenatal developing tissues such as the mid-hindbrain junction. They are also required for the central nervous system (CNS) morphogenesis, limb development and long-bone ossification. Beenken, et al., (2009) have shown that FGF-8 knockout mice fail to undergo gastrulation, whereas FGF-17 knockout mice appear to have developmental aberrations in several brain structures. FGF-18 knockout mice have delayed bone development and poor expression of their osteogenic markers which may point to similarly poor development of osteoblasts.

As with all of the Canonical FGFs, the FGF8 subfamily activates a number of the FGFRs (FGF Receptors), specifically 3c and FGFR4 (4Δ). And while they will also bind to FGFR2c and 1c, it is to a much lesser extent, and they do not prefer any of the FGFRb isoforms at all (Zhang 2006). You can find a more detailed look at the receptor preference of the FGF8 subfamily or an overview of all of the receptor preferences of all of the FGF subfamilies in the JBC online journal.

FGF-18 has also been shown to enhance BMP (Bone Morphogenetic Protein) function and suppress Noggin expression. Noggin is an extracellular protein that normally inhibits the functions of growth factors such as BMP2 or BMP4. FGF-18 suppression of Noggin may help lead to accelerated bone formation and possibly bone repair, and may also compensate for FGF2 suppression in skeletal development and formation. But FGF-18 is also crucial in for various organs as well, such as the liver, small intestine, kidneys and the pancreas and is highly expressed in the lungs and brain.

FGF-8 has been shown to be crucial in the development of the anterior heart field (AHF) (Ilagan 2006) as well as in nephrogenesis, or the development of the kidneys (Grieshammer 2005). In addition, conditions that cause the loss of function of FGF-8 or impair in its receptor binding have been associated with Kallmann Syndrome (Falardeau 2008), which is a genetic condition characterized by hypogonadism.

 

 


Beenken, Andrew, and Moosa Mohammadi. "The FGF family: biology, pathophysiology and therapy." Nature Reviews Drug Discovery 8.3 (2009): 235-253.

Zhang, Xiuqin, et al. "Receptor specificity of the fibroblast growth factor family." Journal of Biological Chemistry 281.23 (2006): 15694-15700.

Haque, T., S. Nakada, and Reggie C. Hamdy. "A review of FGF18: Its expression, signaling pathways and possible functions during embryogenesis and post-natal development." Histology and Histopathology 22 (2007): 97-105.

Ilagan, Roger, et al. "Fgf8 is required for anterior heart field development." Development 133.12 (2006): 2435-2445.

Grieshammer, Uta, et al. "FGF8 is required for cell survival at distinct stages of nephrogenesis and for regulation of gene expression in nascent nephrons." Development 132.17 (2005): 3847-3857.

Falardeau, John, et al. "Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice." Journal of Clinical Investigation 118.8 (2008): 2822-2831.