Abstract
Sensory axons from dorsal root ganglia neurons are guided to spinal targets by molecules differentially expressed along the dorso-ventral axis of the neural tube. NT-3-responsive muscle afferents project ventrally, cease extending, and branch upon contact with motoneurons (MNs), their synaptic partners. We have identified WNT-3 as a candidate molecule that regulates this process. Wnt-3 is expressed by MNs of the lateral motor column at the time when MNs form synapses with sensory neurons. WNT-3 increases branching and growth cone size while inhibiting axonal extension in NT-3- but not NGF-responsive axons. Ventral spinal cord secretes factors with axonal remodeling activity for NT-3-responsive neurons. This activity is present at limb levels and is blocked by a WNT antagonist. We propose that WNT-3, expressed by MNs, acts as a retrograde signal that controls terminal arborization of muscle afferents.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Afferent Pathways / cytology
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Afferent Pathways / embryology*
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Afferent Pathways / metabolism
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Animals
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cell Differentiation / drug effects
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Cell Differentiation / genetics
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Cells, Cultured
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Ganglia, Spinal / cytology
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Ganglia, Spinal / embryology*
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Ganglia, Spinal / metabolism
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Glycogen Synthase Kinase 3
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Glycoproteins / metabolism
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Glycoproteins / pharmacology
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Growth Cones / drug effects
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Growth Cones / metabolism
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Growth Cones / ultrastructure
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Intracellular Signaling Peptides and Proteins
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Mice
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Motor Neurons / cytology
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Motor Neurons / metabolism*
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Nerve Growth Factor / metabolism
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Nerve Growth Factor / pharmacology
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Neural Pathways / cytology
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Neural Pathways / embryology
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Neural Pathways / metabolism
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / genetics
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Neurons, Afferent / cytology
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Neurons, Afferent / drug effects
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Neurons, Afferent / metabolism*
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Neurotrophin 3 / metabolism*
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Neurotrophin 3 / pharmacology
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism*
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Presynaptic Terminals / ultrastructure
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Proteins / antagonists & inhibitors
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Proteins / genetics
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Proteins / metabolism*
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Spinal Cord / cytology
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Spinal Cord / embryology*
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Spinal Cord / metabolism
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Wnt Proteins
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Wnt3 Protein
Substances
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Glycoproteins
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Intracellular Signaling Peptides and Proteins
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Neurotrophin 3
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Proteins
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WD repeat containing planar cell polarity effector
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Wnt Proteins
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Wnt3 Protein
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Wnt3 protein, mouse
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Nerve Growth Factor
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Calcium-Calmodulin-Dependent Protein Kinases
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Glycogen Synthase Kinase 3