title: Differential non-target-derived repulsive signals play a critical role in shaping initial axonal growth of dorsal root ganglion neurons.
abstract: Initial trajectories of dorsal root ganglion (DRG) axons are shaped by chemorepulsive signals from surrounding tissues. Although we have previously shown that axonin-1/SC2 expression on DRG axons is required to mediate a notochord-derived chemorepulsive signal, Dev. Biol. 224, 112-121), other molecules involved in the non-target-derived repulsive signals are largely unknown. Using coculture assays composed of tissues derived from the chick embryo or mutant mice treated with function-blocking antibodies and phosphatidylinositol-specific phospholipase C, we report here that the chemorepellent semaphorin 3A (Sema3A) and its receptor neuropilin-1 are required for mediating the dermamyotome- and notochord-derived, but not the ventral spinal cord-derived, chemorepulsive signal for DRG axons. The dermamyotome-derived chemorepulsion is exclusively dependent on Sema3A/neuropilin-1, whereas other molecules are also involved in the notochord-derived chemorepulsion. Chemorepulsion from the ventral spinal cord does not depend on Sema3A/neuropilin-1 but requires axonin-1/SC2 to repel DRG axons. Thus, differential chemorepulsive signals help shape the initial trajectories of DRG axons and are critical for the proper wiring of the nervous system.
authors.affiliation: Department of Anatomy, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Masuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuji
authors.forename: Masahiko
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yagi
authors.forename: Marc
authors.initials: M
authors.lastname: Tessier-Lavigne
authors.forename: Hajime
authors.initials: H
authors.lastname: Fujisawa
authors.forename: Nobuo
authors.initials: N
authors.lastname: Okado
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiga
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D019556:COS Cells; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology; D002633:Chemotaxis / Q000502:physiology*; D002642:Chick Embryo; D058969:Contactin 2; D005727:Ganglia, Spinal / Q000502:physiology*; D039942:Neuropilin-1 / Q000502:physiology*; D009672:Notochord / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D040121:Semaphorin-3A / Q000235:genetics / Q000502:physiology*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C548675:Cntn2 protein, mouse; D058969:Contactin 2; D012333:RNA, Messenger; D040121:Semaphorin-3A; D039942:Neuropilin-1