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.
Elvers
Margitta
M
Institut für Neurobiochemie, Universität Witten/Herdecke, Stockumer Strreet, 10, Witten D-58448, Germany.
Pfeiffer
Julia
J
Kaltschmidt
Christian
C
Kaltschmidt
Barbara
B
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000196:embryology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D046509:Tissue Culture Techniques; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053781:Transforming Growth Factor beta2
D061945:Caspase Inhibitors; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D020169:Caspases