Transforming growth factor beta1 modulates cell migration in rat cortex: effects of ethanol

Transforming growth factor (TGF) beta1 regulates cell migration of non-neural cells. Hence, two hypotheses were tested: (i) that TGFbeta1 affects cell migration and the expression of associated adhesion proteins in developing cortex; and (ii) that these effects are antagonized by ethanol. The effects of TGFbeta1 (2.5-40 ng/ml) and ethanol (400 mg/dl) on cell migration were examined in organotypic cultures from fetal rat brains. Migration was determined by tracing the movement of cells pulse-labeled with bromodeoxyuridine. Cell migration was altered by TGFbeta1 in a concentration-dependent manner: at low concentrations, cell migration was promoted whereas at high concentrations TGFbeta1 impeded migration. Ethanol treatment alone reduced the rate of migration. Interestingly, the rate of cell migration in slices treated with both TGFbeta1 and ethanol was the same as that in untreated cultures. The expression of cell adhesion proteins (nCAM, integrin alpha3, alphav and beta1) was differentially effected by TGFbeta1 and/or ethanol. TGFbeta1 increased the expression of these adhesion proteins in a progressive, concentration-dependent manner. Likewise, ethanol also increased adhesion protein expression, however, combined TGFbeta1 and ethanol treatment reduced expression. Collectively, the data show that TGFbeta1 alters cell migration in the developing cortex and that the TGFbeta1 system is a target of ethanol toxicity.