title: The Yin and Yang of Wnt/Ryk axon guidance in development and regeneration.
abstract: In the developing embryo, nascent axons navigate towards their specific targets to establish the intricate network of axonal connections linking neurons within the mature nervous system. Molecular navigational systems comprising repulsive and attractive guidance cues form chemotactic gradients along the pathway of the exploring growth cone. Axon-bound receptors detect these gradients and determine the trajectory of the migrating growth cone. In contrast to their benevolent role in the developing nervous system, repulsive guidance receptors are detrimental to the axon's ability to regenerate after injury in the adult. In this review we explore the essential and beneficial role played by the chemorepulsive Wnt receptor, Ryk/Derailed in axon navigation in the embryonic nervous system (the Yin function). Specifically, we focus on the role of Wnt5a/Rykmediated guidance in the establishment of two major axon tracts in the mammalian central nervous system, the corticospinal tract and the corpus callosum. Recent studies have also identified Ryk as a major suppressor of axonal regeneration after spinal cord injury. Thus, we also discuss this opposing aspect of Ryk function in axonal regeneration where its activity is a major impediment to axon regrowth (the Yang function).
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, 4072, Australia.
authors.forename: Charlotte E J
authors.initials: CE
authors.lastname: Clark
authors.forename: Yaobo
authors.initials: Y
authors.lastname: Liu
authors.forename: Helen M
authors.initials: HM
authors.lastname: Cooper
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology*; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003337:Corpus Callosum / Q000196:embryology / Q000378:metabolism; D015509:Developmental Biology; D004330:Drosophila / Q000502:physiology; D029721:Drosophila Proteins / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D009416:Nerve Regeneration; D009420:Nervous System / Q000196:embryology; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000473:pathology; D013997:Time Factors; D051153:Wnt Proteins / Q000378:metabolism; D000071818:Wnt-5a Protein
chemical_list: D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C094492:DRL protein, Drosophila; C080836:RYK protein, human; D020794:Receptor Protein-Tyrosine Kinases; C118148:Ryk protein, mouse; D002118:Calcium