Transforming growth factor-β2 both stimulates and inhibits neurogenesis of rat cerebellar granule cells in culture

Abstract

Transforming growth factor-β2 (TGFβ2) is expressed in the developing cerebellar cortex during the period of granule cell proliferation and maturation. However, the role of TGFβ2 in granule cell development is confused by conflicting observations regarding TGFβ2 control of neurogenesis. To resolve these conflicts and determine the effect of TGFβ2 on neurogenesis, rat cerebellar granule cell cultures were treated with TGFβ2 (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. TGFβ2 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, TGFδ2 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 TGFβ2 activity. Thus, TGFβ2 differentially regulates neurogenesis of cerebellar granule cells depending on the presence of exogenous, undefined regulatory factors derived from serum. This suggests that TGFβ2 activity in cerebellar neurogenesis is complex as it may be modulated by the repertoire of other endogenous regulatory factors in the developing cerebellar cortex.