TGF-beta2 neutralization inhibits proliferation and activates apoptosis of cerebellar granule cell precurors in the developing cerebellum

Transforming growth factor beta 2 (TGF-beta2) plays a critical role in growth, differentiation and cell death, but its function in the developing cerebellum is still uncertain. In this study we analyzed the effects of TGF-beta2 on ex vivo developing cerebellar slice cultures. Proliferation of granule cell precursors peaked ex vivo in the same developmental window as in vivo (P8-P14). Addition of recombinant TGF-beta2 could extent the proliferation of granule cell precursors and induced a second late proliferation wave. In contrast, antibody neutralization of TGF-beta2 strongly reduced proliferation and induced neurodegeneration. TGF-beta2 neutralization resulted in apoptotic cells, which showed caspase 3 activation. Taken together our results demonstrate that TGF-beta2 is a novel growth and survival factor for granule cells precursors in the developing cerebellum.