Involvement of Gas7 in nerve growth factor-independent and dependent cell processes in PC12 cells

Gas7, a growth arrest-specific gene originally isolated from serum-starved mouse fibroblast cells, is expressed in vivo predominantly in the brain and is required for neurite formation in cultured mouse cerebellar neurons (Ju et al. [1998] Proc. Natl. Acad. Sci. USA 95: 11423-11428). Here we report that Gas7 plays a key role in the morphological differentiation of PC12 preneuronal rat pheochromocytoma cells (PC12 cells). We found that overexpression of murine Gas7 in PC12 cells leads to an expanded cell morphology and promotes spike-like cell processes that resemble the early stages of neurite formation. These processes undergo elongation upon addition of nerve growth factor (NGF). We also found that the addition of NGF induces the production of endogenous rat-Gas7 (rGas7), which is transiently elevated prior to the appearance of NGF-promoted neurite outgrowths. Furthermore, inhibition of endogenous rGas7 production by antisense nucleotides complimentary to the translation initiation region of a rGas7 cDNA (AJ131902) reduces the NGF-promoted neurite outgrowths. Our results demonstrate that Gas7 by itself influences early cell morphological development and likely functions as an early-stage intermediary in NGF-induced neuronal differentiation of PC12 culture cells.