RT Journal Article SR Electronic T1 Tonic Activation of Bax Primes Neural Progenitors for Rapid Apoptosis through a Mechanism Preserved in Medulloblastoma JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 18098 OP 18108 DO 10.1523/JNEUROSCI.2602-13.2013 VO 33 IS 46 A1 Andrew J. Crowther A1 Vivian Gama A1 Ariana Bevilacqua A1 Sha X. Chang A1 Hong Yuan A1 Mohanish Deshmukh A1 Timothy R. Gershon YR 2013 UL http://www.jneurosci.org/content/33/46/18098.abstract AB Commitment to survival or apoptosis within expanding progenitor populations poses distinct risks and benefits to the organism. We investigated whether specialized mechanisms regulate apoptosis in mouse neural progenitors and in the progenitor-derived brain tumor medulloblastoma. Here, we identified constitutive activation of proapoptotic Bax, maintained in check by Bcl-xL, as a mechanism for rapid cell death, common to postnatal neural progenitors and medulloblastoma. We found that tonic activation of Bax in cerebellar progenitors, along with sensitivity to DNA damage, was linked to differentiation state. In cerebellar progenitors, active Bax localized to mitochondria, where it was bound to Bcl-xL. Disruption of Bax:Bcl-xL binding by BH3-mimetic ABT 737 caused rapid apoptosis of cerebellar progenitors and primary murine medulloblastoma cells. Conditional deletion of Mcl-1, in contrast, did not cause death of cerebellar progenitors. Our findings identify a mechanism for the sensitivity of brain progenitors to typical anticancer therapies and reveal that this mechanism persists in medulloblastoma, a malignant brain tumor markedly sensitive to radiation and chemotherapy.