Differential Non-Target-Derived Repulsive Signals Play a Critical Role in Shaping Initial Axonal Growth of Dorsal Root Ganglion Neurons

Dev Biol. 2003 Feb 15;254(2):289-302. doi: 10.1016/s0012-1606(02)00087-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / physiology*
  • COS Cells
  • Cell Adhesion Molecules, Neuronal / physiology
  • Chemotaxis / physiology*
  • Chick Embryo
  • Contactin 2
  • Ganglia, Spinal / physiology*
  • Neuropilin-1 / physiology*
  • Notochord / physiology
  • RNA, Messenger / analysis
  • Semaphorin-3A / genetics
  • Semaphorin-3A / physiology*

Substances

  • Cell Adhesion Molecules, Neuronal
  • Cntn2 protein, mouse
  • Contactin 2
  • RNA, Messenger
  • Semaphorin-3A
  • Neuropilin-1