Transforming growth factor-beta 2 both stimulates and inhibits neurogenesis of rat cerebellar granule cells in culture.

Transforming growth factor-beta 2 (TGF beta 2) is expressed in the developing cerebellar cortex during the period of granule cell proliferation and maturation. However, the role of TGF beta 2 in granule cell development is confused by conflicting observations regarding TGF beta 2 control of neurogenesis. To resolve these conflicts and determine the effect of TGF beta 2 on neurogenesis, rat cerebellar granule cell cultures were treated with TGF beta 2 (0.1-100 ng/ml, 24 h) in the presence or absence of exogenous serum. Neuroblast proliferation was quantified by bromodeoxyuridine and [3H]thymidine incorporation. TGF beta 2 stimulated proliferation to 220% of controls in the presence of serum (ED50 = 0.4 ng/ml) based on bromodeoxyuridine labeled granule cell counts. In contrast, in serum free medium, TGF beta 2 inhibited proliferation 75% (ED50 = 0.7 ng/ml). DNA synthesis measured by [3H]thymidine incorporation was increased to 122% in the presence of serum factors, but inhibited 70% in serum free medium, as a result of TGF beta 2 activity. Thus, TGF beta 2 differentially regulates neurogenesis of cerebellar granule cells depending on the presence of exogenous, undefined regulatory factors derived from serum. This suggests that TGF beta 2 activity in cerebellar neurogenesis is complex as it may be modulated by the repertoire of other endogenous regulatory factors in the developing cerebellar cortex.