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Cerebral Cortex Advance Access originally published online on April 14, 2004
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Cerebral Cortex July 2004; 14:791-802
© Oxford University Press 2004

Article

Transforming Growth Factor ß1 Modulates Cell Migration in Rat Cortex: Effects of Ethanol

Julie A. Siegenthaler1 and Michael W. Miller1,2

1 Department of Neuroscience and Physiology, State University of New York- Upstate Medical University, Syracuse, NY 13210, USA, 2 Research Service, Veterans Affairs Medical Center, Syracuse, NY 13210, USA

Transforming growth factor (TGF) ß1 regulates cell migration of non-neural cells. Hence, two hypotheses were tested: (i) that TGFß1 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 TGFß1 (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 TGFß1 in a concentration-dependent manner: at low concentrations, cell migration was promoted whereas at high concentrations TGFß1 impeded migration. Ethanol treatment alone reduced the rate of migration. Interestingly, the rate of cell migration in slices treated with both TGFß1 and ethanol was the same as that in untreated cultures. The expression of cell adhesion proteins (nCAM, integrin {alpha}3, {alpha}v and ß1) was differentially effected by TGFß1 and/or ethanol. TGFß1 increased the expression of these adhesion proteins in a progressive, concentration-dependent manner. Likewise, ethanol also increased adhesion protein expression, however, combined TGFß1 and ethanol treatment reduced expression. Collectively, the data show that TGFß1 alters cell migration in the developing cortex and that the TGFß1 system is a target of ethanol toxicity.


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