Neuromuscular Development after the Prevention of Naturally Occurring Neuronal Death by Bax Deletion

• DOI: 10.1523/jneurosci.23-19-07298.2003
• Publication Date: 2018-04-13T22:30:28Z
• Authors: Woong Sun; Thomas W. Gould; Sharon Vinsant; David Prevette; Ronald W. Oppenheim
• Keywords: Mice, Knockout; Motor Neurons; 0301 basic medicine; Models, Neurological; Neuromuscular Junction; Apoptosis; Nervous System; Axons; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Animals, Newborn; Proto-Oncogene Proteins c-bcl-2; Ganglia, Spinal; Proto-Oncogene Proteins; Animals; Glial Cell Line-Derived Neurotrophic Factor; Nerve Growth Factors; Atrophy; Muscle, Skeletal; Cell Division; bcl-2-Associated X Protein

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) inBaxknock-out (BaxKO) mice fail to undergo PCD in the face of normal target muscle development, we asked whether the excess rescued neurons inBaxKO mice can develop normally. We observed many small atrophied MNs in postnatalBaxKO 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 inBaxKO 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 byBaxdeletion, 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 byBaxdeletion, their subsequent development is less affected than that of MNs.