Neuromuscular development after the prevention of naturally occurring neuronal death by Bax deletion

Woong Sun, Thomas W. Gould, Sharon Vinsant, David Prevette, Ronald W. Oppenheim

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58 Citations (Scopus)

Abstract

The removal of excess neurons by programmed cell death (PCD) is believed to be critical for the proper development and function of the nervous system. A major role of this neuronal loss is to attain quantitative matching of neurons with their targets and afferents. Because motoneurons (MNs) in Bax knock-out (Bax KO) mice fail to undergo PCD in the face of normal target muscle development, we asked whether the excess rescued neurons in Bax KO mice can develop normally. We observed many small atrophied MNs in postnatal Bax KO mice, and these failed to innervate limb muscle targets. When examined embryonically during the PCD period, however, these excess MNs had initiated target innervation. To examine whether a limitation in trophic factor availability is responsible for postnatal MN atrophy and loss of innervation, we applied glial cell line-derived neurotrophic factor (GDNF) to neonatal mice. GDNF injection for 7-14 d induced the regrowth and reinnervation of muscle targets by atrophic MNs in Bax KO mice and prevented the normal postnatal death of MNs in wild-type mice. These results indicate that, although initially all of the MNs, including those rescued by Bax deletion, are able to project to and innervate targets, because of limited target-derived signals required for maintaining innervation and growth, only a subpopulation can grow and retain target contacts postnatally. Although sensory neurons in the dorsal root ganglia are also rescued from PCD by Bax deletion, their subsequent development is less affected than that of MNs.

Original languageEnglish
Pages (from-to)7298-7310
Number of pages13
JournalJournal of Neuroscience
Volume23
Issue number19
Publication statusPublished - 2003 Aug 13
Externally publishedYes

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Keywords

  • Bax
  • Cell death
  • Innervation
  • Motoneurons
  • Mouse
  • Spinal cord
  • Target dependence

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Sun, W., Gould, T. W., Vinsant, S., Prevette, D., & Oppenheim, R. W. (2003). Neuromuscular development after the prevention of naturally occurring neuronal death by Bax deletion. Journal of Neuroscience, 23(19), 7298-7310.