Roles of intracellular fibroblast growth factors in neural development and functions.

Fibroblast growth factors (FGFs) can be classified as secretory (FGF1-10 and FGF15-23) or intracellular non-secretory forms (FGF11-14). Secretory forms of FGF and their receptors are best known for their regulatory roles in cell growth, differentiation and morphogenesis in the early stages of neural development. However, the functions of intracellular FGFs remain to be explored. FGF12 and FGF14 are found to interact with voltage-gated sodium channels, and regulate the channel activity in neurons. FGF13 is expressed in primary sensory neurons, and is colocalized with sodium channels at the nodes of Ranvier along the myelinated afferent fibers. FGF13 is also expressed in cerebral cortical neurons during the late developmental stage. A recent study showed that FGF13 is a microtubule-stabilizing protein required for regulating the neuronal development in the cerebral cortex. Thus, non-secretory forms of FGF appear to have important roles in the brain, and it would be interesting to further investigate the functions of intracellular FGFs in the nervous system and in neural diseases.