Abstract
Guidance cues along the longitudinal axis of the CNS are poorly understood. Wnt proteins attract ascending somatosensory axons to project from the spinal cord to the brain. Here we show that Wnt proteins repel corticospinal tract (CST) axons in the opposite direction. Several Wnt genes were found to be expressed in the mouse spinal cord gray matter, cupping the dorsal funiculus, in an anterior-to-posterior decreasing gradient along the cervical and thoracic cord. Wnts repelled CST axons in collagen gel assays through a conserved high-affinity receptor, Ryk, which is expressed in CST axons. Neonatal spinal cord secretes diffusible repellent(s) in an anterior-posterior graded fashion, with anterior cord being stronger, and the repulsive activity was blocked by antibodies to Ryk (anti-Ryk). Intrathecal injection of anti-Ryk blocked the posterior growth of CST axons. Therefore, Wnt proteins may have a general role in anterior-posterior guidance of multiple classes of axons.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Axons / physiology
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Body Patterning / drug effects
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Body Patterning / physiology*
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Carbocyanines / metabolism
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Carrier Proteins / physiology
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Cell Line
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Chlorocebus aethiops
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Coculture Techniques / methods
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Embryo, Mammalian
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Gene Expression Regulation, Developmental
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Humans
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Immunohistochemistry / methods
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In Situ Hybridization / methods
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Intercellular Signaling Peptides and Proteins / classification
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Intercellular Signaling Peptides and Proteins / pharmacology
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Intercellular Signaling Peptides and Proteins / physiology*
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Leukocyte L1 Antigen Complex / metabolism
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Mice
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Nerve Tissue Proteins / metabolism
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Organ Culture Techniques / methods
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Pyramidal Tracts / embryology*
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Pyramidal Tracts / growth & development*
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Receptor Protein-Tyrosine Kinases / physiology*
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Signal Transduction / physiology
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Spinal Cord / embryology
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Spinal Cord / metabolism
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Transfection / methods
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Wnt Proteins
Substances
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3,3'-dihexadecylindocarbocyanine
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Carbocyanines
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Carrier Proteins
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Intercellular Signaling Peptides and Proteins
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Leukocyte L1 Antigen Complex
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Nerve Tissue Proteins
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Wnt Proteins
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Receptor Protein-Tyrosine Kinases
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Ryk protein, mouse