Back to Search Start Over

Neuromuscular Development in the Absence of Programmed Cell Death: Phenotypic Alteration of Motoneurons and Muscle

Authors :
Ronald W. Oppenheim
David Prevette
Adam K. Winseck
Robert R. Buss
Jianjun Ma
Kimberly A. Toops
Thomas L. Smith
Thomas W. Gould
Sharon Vinsant
James A Hammarback
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.

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