Trial of regeneration of retinal neuronal cells by myoseverin

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Myoseverin is a microtubule-binding molecule that induces the dedifferentiation of C2C12 myotubes to individual muscle cells. Here we present the trial of the neural cell regeneration by myoseverin.1) Rat pheochromocytoma PC12 cells differentiate to nerve cells by nerve growth factor (NGF). Addition of myoseverin did not promote of dedifferentiation of NGF-treated PC12 cells. However, when myoseverin was added simultaneously with NGF to PC12 cells, extension of axons was inhibited in about 15% cells. But they did not proliferate and finally exhibited apoptic cell death.2) The induction of RalGDS has been known to inhibit the NGF-induced differentiation of PC12 cells. We found that myoseverin induced the mRNA of RalGDS in PC12 cells. Thus, RalGDS might play an important role in inhibiting NGF-induced differentiation.3) We tried to clone the additional myoseverin-induced genes in PC12 cells and ribosomal PO gene, cofilin and GADD45β were cloned. We established the individual PC12 cell lines that stably expressed those genes and examined their response to NGF. Those cell lines, however, differentiated upon NGF stimulation as parental PC12 cells.4) Retinal pigment epithelial (RPE) cells of rat embryo at day 12 of gestation were cultured in vitro. Basic fibroblast growth factor (bFGF) induced cell proliferation, suppressed their pigmentation, and increased the expression of CHX10 and nestin that were molecular markers of neural progenitors. Myoseverin enhanced these bFGF effects up to about 30%.5) Although bFGF induced the expression of glial fibrillary acidic protein (GFAP) that was a molecular marker of Muller glial cells after 7 days culture, addition of myoseverin inhibited the induction.Thus, while myoseverin has a cooperative effect on the transdifferentiation of RPE induced by bFGF during an initial stage, probably its toxicity inhibited their further differentiation to mature neural cells.