Widespread elimination of naturally occurring neuronal death in Bax- deficient mice

Fletcher A. White, Cynthia R. Keller-Peck, C. Michael Knudson, Stanley J. Korsmeyer, William D. Snider

Research output: Contribution to journalArticle

349 Scopus citations

Abstract

The proapoptotic molecule BAX is required for death of sympathetic and motor neurons in the setting of trophic factor deprivation. Furthermore, adult Bax-/- mice have more motor neurons than do their wild-type counterparts. These findings raise the possibility that BAX regulates naturally occurring cell death during development in many neuronal populations. To test this idea, we assessed apoptosis using TUNEL labeling in several well-studied neural systems during embryonic and early postnatal development in Bax-/- mice. Remarkably, naturally occurring cell death is virtually eliminated between embryonic day 11.5 (E11.5) and postnatal day 1 (PN1) in most peripheral ganglia, in motor pools in the spinal cord, and in the trigeminal brainstem nuclear complex. Additionally, reduction, although not elimination, of cell death was noted throughout the developing cerebellum, in some layers of the retina, and in the hippocampus. Saving of cells was verified by axon counts of dorsal and ventral roots, as well as facial and optic nerves that revealed 24-35% increases in axon number. Interestingly, many of the supernumerary axons had very small cross-sectional areas, suggesting that the associated neurons are not normal. We conclude that BAX is a critical mediator of naturally occurring death of peripheral and CNS neurons during embryonic life. However, rescue from naturally occurring cell death does not imply that the neurons will develop normal functional capabilities.

Original languageEnglish (US)
Pages (from-to)1428-1439
Number of pages12
JournalJournal of Neuroscience
Volume18
Issue number4
StatePublished - Feb 15 1998
Externally publishedYes

Keywords

  • Apoptosis
  • BAX
  • Bcl-2 gene family
  • Motor neuron
  • Primary afferent neurons
  • Programmed cell death

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    White, F. A., Keller-Peck, C. R., Michael Knudson, C., Korsmeyer, S. J., & Snider, W. D. (1998). Widespread elimination of naturally occurring neuronal death in Bax- deficient mice. Journal of Neuroscience, 18(4), 1428-1439.