Anterior-Posterior Guidance of Commissural Axons by Wnt-Frizzled Signaling

• Published in: Science (American Association for the Advancement of Science) 2003-12, Vol.302 (5652), p.1984-1988
• Main Authors: Lyuksyutova, Anna I., Lu, Chin-Chun, Milanesio, Nancy, King, Leslie A., Guo, Nini, Wang, Yanshu, Nathans, Jeremy, Tessier-Lavigne, Marc, Zou, Yimin
• Format: Article
• Language: English
• Subjects: Animals; Axons; Axons - physiology; Axons - ultrastructure; Biological and medical sciences; Brain - embryology; Brain - metabolism; Central Nervous System - cytology; Central Nervous System - embryology; Central Nervous System - metabolism; Collagens; COS Cells; Cues; Culture Techniques; Diffusion; Embryos; Frizzled Receptors; Frizzled3 protein; Fundamental and applied biological sciences. Psychology; Gels; Gene Expression Profiling; Growth cones; Growth Cones - physiology; Growth Cones - ultrastructure; Guidance; House mouse; In Situ Hybridization; Membrane Proteins; Mice; Mice as laboratory animals; Mice, Knockout; Nervous system; Neurology; Neurons; Neurons - physiology; Neuroscience; Neurotransmitters; Population Distribution; Proteins - pharmacology; Proto-Oncogene Proteins - metabolism; Quantification; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Signal Transduction; Signaling; Signals and signaling; Spinal cord; Spinal Cord - cytology; Spinal Cord - embryology; Spinal Cord - metabolism; Stimuli; Transfection; Vertebrates: nervous system and sense organs; Wnt Proteins; Wnt4 gene; Wnt4 Protein
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1089610

Commissural neurons in the mammalian dorsal spinal cord send axons ventrally toward the floor plate, where they cross the midline and turn anteriorly toward the brain; a gradient of chemoattractant(s) inside the spinal cord controls this turning. In rodents, several Wnt proteins stimulate the extension of commissural axons after midline crossing (postcrossing). We found that Wnt4 messenger RNA is expressed in a decreasing anterior-to-posterior gradient in the floor plate, and that a directed source of Wnt4 protein attracted postcrossing commissural axons. Commissural axons in mice lacking the Wnt receptor Frizzled3 displayed anterior-posterior guidance defects after midline crossing. Thus, Wnt-Frizzled signaling guides commissural axons along the anterior-posterior axis of the spinal cord.