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The Journal of Neuroscience, December 3, 2003, 23(35):11112-11119

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Cellular/Molecular
The Proapoptotic Activities of Bax and Bak Limit the Size of the Neural Stem Cell Pool

Tullia Lindsten,^1,4 * Jeffrey A. Golden,^1,5 * Wei-Xing Zong,^3,4 Jeremy Minarcik,^1,5 Marian H. Harris,^3,4 and Craig B. Thompson^2,3,4

Departments of ¹Pathology and Laboratory Medicine, ²Medicine, and ³Cancer Biology and ⁴Abramson Family Cancer Research Institute, University of Pennsylvania, and ⁵The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104

The proapoptotic Bcl-2 family members Bak and Bax play central and redundant roles in the regulation of apoptosis. In this study, we investigated the effect of loss of Bax and Bak in the CNS. The adult bax^-/-bak^-/- mice display masses of densely staining cells in the proliferative zones of the brain. These cells are shown to be a mix of neural progenitor cells and postmitotic cells at different stages of neural and glial differentiation. Both neural progenitor cells and mature neurons derived from bax^-/-bak^-/- mice were resistant to various apoptotic stimuli. Despite this resistance, postmitotic mature bax^-/-bak^-/- neurons remain as sensitive to excitoxic death as wild-type neurons. Thus, Bax and Bak play a critical role in regulating the number of neural progenitor cells in the adult brain but are not absolutely required for the initiation of neuronal cell death after neurotoxic injury.

Key words: Bax; Bak; neural progenitor cells; proliferative zones; apoptosis; excitotoxicity

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Received May 22, 2003; revised October 9, 2003; accepted October 9, 2003.

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