FGF8 Activates Proliferation and Migration in Mouse Post-Natal Oligodendrocyte Progenitor Cells

Abstract

Fibroblast growth factor 8 (FGF8) is a key molecular signal that is necessary for early embryonic development of the central nervous system, quickly disappearing past this point. It is known to be one of the primary morphogenetic signals required for cell fate and survival processes in structures such as the cerebellum, telencephalic and isthmic organizers, while its absence causes severe abnormalities in the nervous system and the embryo usually dies in early stages of development. In this work, we have observed a new possible therapeutic role for this factor in demyelinating disorders, such as leukodystrophy or multiple sclerosis. In vitro, oligodendrocyte progenitor cells were cultured with differentiating medium and in the presence of FGF8. Differentiation and proliferation studies were performed by immunocytochemistry and PCR. Also, migration studies were performed in matrigel cultures, where oligodendrocyte progenitor cells were placed at a certain distance of a FGF8-soaked heparin bead. The results showed that both migration and proliferation was induced by FGF8. Furthermore, a similar effect was observed in an in vivo demyelinating mouse model, where oligodendrocyte progenitor cells were observed migrating towards the FGF8-soaked heparin beads where they were grafted. In conclusion, the results shown here demonstrate that FGF8 is a novel factor to induce oligodendrocyte progenitor cell activation, migration and proliferation in vitro, which can be extrapolated in vivo in demyelinated animal models.

Mechanisms of oligodendrocyte progenitor developmental migration

“…HGF induces OPC process extension and increased actin and β‐tubulin expression (Yan & Rivkees, 2002), but the relevance of this pathway in vivo remains unclear. Fibroblast growth factor 8 (FGF8) has also been suggested to induce OPC migration in vitro (Cruz‐Martinez et al., 2014).…”

Highly Effective Protocol for Differentiation of Induced Pluripotent Stem Cells (iPS) into Melanin-Producing Cells

“…Comparing with other published protocols [ 8 , 9 , 10 , 37 , 38 , 39 ], we have found that melanocyte induction media contain, e.g., BMP-4, Wnt3a, Endothelin, or SCF, but none of them were supplemented with FGF-8. FGF-8 plays an important role in the regulation of embryonic development, cell proliferation, and cell migration and differentiation, especially the differentiation of oligodendrocyte progenitor cells [ 40 ]. It has been shown that during embryogenesis, FGF-8 expression increases in neuroepithelium, which is a common precursor for midbrain and pigmented cells (i.e., RPE cells) [ 41 ].…”

Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1

“…Our data suggest that MIF may aid regeneration after CNS injury, by inhibiting HTRA1 that is continuously secreted from cells. An increase of MIF thus contributes to the increase of growth factors, such as FGF8, FGF18 and TGF-β that in turn can increase astrocyte and oligodendrocyte migration and proliferation as well as neural protection [ 75 – 77 ].…”