TGF-alpha induces a stationary, radial-glia like phenotype in cultured astrocytes

Transgenic mice studies have suggested that transforming growth factor-alph a (TGF-alpha) influences the postnatal differentiation of astrocytes. To un derstand the role of TGF-alpha during astrocytic differentiation, it is imp ortant to determine how this factor affects astrocytes in the absence of ot her influences. We have thus examined in vitro under serum-free medium cond itions the effect of TGF-alpha on the properties of astrocytes derived from the cerebral cortex of newborn rats. When TGF-alpha is added to serum-free medium, most astrocytes lose their polygonal shape and extend two long pro cesses running in opposite directions. This bipolar morphology strikingly r esembles that of radial glial cells. Intriguingly, serum inhibits this morp hological transformation. TGF-alpha also triggers an increase in glial fibr illary acidic protein (GFAP) expression and a decrease in nestin expression . Another major effect of TGF-alpha is to practically abolish the motility of astrocytes. TGF-alpha, however, does not appear to influence the prolife ration and apoptosis of astrocytes. These results suggest that polygonal as trocytes are derived primarily from radial glial cells, and that in vivo TG F-alpha may be instrumental in determining the shape and migratory potentia l of radial glial cells. (C) 2001 Elsevier Science Inc.