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Neuromuscular Development in the Absence of Programmed Cell Death: Phenotypic Alteration of Motoneurons and Muscle
- Source :
- The Journal of Neuroscience. 26:13413-13427
- Publication Year :
- 2006
- Publisher :
- Society for Neuroscience, 2006.
-
Abstract
- The widespread, massive loss of developing neurons in the central and peripheral nervous system of birds and mammals is generally considered to be an evolutionary adaptation. However, until recently, models for testing both the immediate and long-term consequences of preventing this normal cell loss have not been available. We have taken advantage of several methods for preventing neuronal deathin vivoto ask whether rescued neurons [e.g., motoneurons (MNs)] differentiate normally and become functionally incorporated into the nervous system. Although many aspects of MN differentiation occurred normally after the prevention of cell death (including the expression of several motoneuron-specific markers, axon projections into the ventral root and peripheral nerves, ultrastructure, dendritic arborization, and afferent axosomatic synapses), other features of the neuromuscular system (MNs and muscle) were abnormal. The cell bodies and axons of MNs were smaller than normal, many MN axons failed to become myelinated or to form functional synaptic contacts with target muscles, and a subpopulation of rescued cells were transformed from α- to γ-like MNs. Additionally, after the rescue of MNs in myogenin glial cell line-derived neurotrophic factor (MyoGDNF) transgenic mice, myofiber differentiation of extrafusal skeletal muscle was transformed and muscle physiology and motor behaviors were abnormal. In contrast, extrafusal myofiber phenotype, muscle physiology, and (except for muscle strength tests) motor behaviors were all normal after the rescue of MNs by genetic deletion of the proapoptotic geneBax. However, there was an increase in intrafusal muscle fibers (spindles) inBaxknock-out versus both wild-type andMyoGDNFmice. Together, these data indicate that after the prevention of MN death, the neuromuscular system becomes transformed in novel ways to compensate for the presence of the thousands of excess cells.
- Subjects :
- Male
Nervous system
Programmed cell death
Apoptosis
Mice, Transgenic
Chick Embryo
Biology
Mice
Neurotrophic factors
medicine
Animals
Myocyte
Axon
Muscle, Skeletal
Myogenin
Cell Size
bcl-2-Associated X Protein
Mice, Knockout
Motor Neurons
General Neuroscience
Skeletal muscle
Articles
Axons
Mice, Inbred C57BL
Phenotype
medicine.anatomical_structure
nervous system
Peripheral nervous system
Mice, Inbred CBA
Female
Neuroscience
Subjects
Details
- ISSN :
- 15292401 and 02706474
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- The Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....934b79b98c556ba89ba65f8948b52b5a
- Full Text :
- https://doi.org/10.1523/jneurosci.3528-06.2006