TY - JOUR T1 - TGF-β-Induced Apoptosis of Cerebellar Granule Neurons Is Prevented by Depolarization JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4174 LP - 4185 DO - 10.1523/JNEUROSCI.16-13-04174.1996 VL - 16 IS - 13 AU - Ariane de Luca AU - Michael Weller AU - Adriano Fontana Y1 - 1996/07/01 UR - http://www.jneurosci.org/content/16/13/4174.abstract N2 - The regulation of programmed cell death in the developing nervous system involves target-derived survival factors, afferent synaptic activity, and hormone- and cytokine-dependent signaling. Cultured immature cerebellar granule neurons die by apoptosis within several days in vitro unless maintained in depolarizing (high) concentrations of potassium (25 mmK+). Here we report that transforming growth factors (TGF)-β1, -β2, and -β3 accelerate apoptosis of these neurons when maintained in physiological (low) K+ medium (5 mm K+) as assessed by measures of viability, quantitative DNA fragmentation, and nuclear morphology. TGF-β-induced apoptosis of these neurons is not blocked by CNTF and LIF, cytokines that enhance neuronal survival when applied alone, or by IGF-I, which prevents apoptosis upon potassium withdrawal. In contrast, neurons that differentiate in high K+ medium for several days in vitroacquire resistance to TGF-β-mediated cell death. Granule neurons maintained in either low or high K+ medium produce latent, but not bioactive, TGF-β1 and -β2. Because neutralizing TGF-β antibodies fail to augment survival of low K+ neurons, the cerebellar neurons are apparently unable to activate latent TGF-β. Thus, apoptosis of low K+ neurons is not attributable to endogenous production of TGF-β. Taken together, our data suggest that TGF-β may limit the expansion of postmitotic neuronal precursor populations by promoting their apoptosis but may support survival of those neurons that have maturated, differentiated, and established supportive synaptic connectivity. ER -