Abstract
DNA topoisomerase IIbeta is shown to have an unsuspected and critical role in neural development. Neurogenesis was normal in IIbeta mutant mice, but motor axons failed to contact skeletal muscles, and sensory axons failed to enter the spinal cord. Despite an absence of innervation, clusters of acetylcholine receptors were concentrated in the central region of skeletal muscles, thereby revealing patterning mechanisms that are autonomous to skeletal muscle. The defects in motor axon growth in IIbeta mutant mice resulted in a breathing impairment and death of the pups shortly after birth.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Axons / physiology*
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Axons / ultrastructure
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Cell Lineage
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Cues
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DNA Repair
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DNA Topoisomerases, Type II / genetics
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DNA Topoisomerases, Type II / metabolism*
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DNA-Binding Proteins
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Diaphragm / chemistry
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Diaphragm / embryology
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Diaphragm / innervation
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Embryonic and Fetal Development
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Gene Targeting
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Intercostal Muscles / innervation
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Mice
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Mice, Knockout
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Motor Neurons / physiology
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Motor Neurons / ultrastructure
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Muscle, Skeletal / embryology
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Muscle, Skeletal / innervation*
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Neuromuscular Junction / embryology*
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Neuromuscular Junction / growth & development
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Neurons, Afferent / physiology
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Neurons, Afferent / ultrastructure
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Presynaptic Terminals / ultrastructure
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Receptors, Cholinergic / analysis
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Skin / innervation
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Spinal Cord / embryology
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Spinal Cord / ultrastructure
Substances
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DNA-Binding Proteins
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Receptors, Cholinergic
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DNA Topoisomerases, Type II