Emergent growth cone responses to combinations of Slit1 and Netrin 1 in thalamocortical axon topography

Curr Biol. 2011 Oct 25;21(20):1748-55. doi: 10.1016/j.cub.2011.09.008. Epub 2011 Oct 13.

Abstract

How guidance cues are integrated during the formation of complex axonal tracts remains largely unknown. Thalamocortical axons (TCAs), which convey sensory and motor information to the neocortex, have a rostrocaudal topographic organization initially established within the ventral telencephalon [1-3]. Here, we show that this topography is set in a small hub, the corridor, which contains matching rostrocaudal gradients of Slit1 and Netrin 1. Using in vitro and in vivo experiments, we show that Slit1 is a rostral repellent that positions intermediate axons. For rostral axons, although Slit1 is also repulsive and Netrin 1 has no chemotactic activity, the two factors combined generate attraction. These results show that Slit1 has a dual context-dependent role in TCA pathfinding and furthermore reveal that a combination of cues produces an emergent activity that neither of them has alone. Our study thus provides a novel framework to explain how a limited set of guidance cues can generate a vast diversity of axonal responses necessary for proper wiring of the nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / physiology*
  • COS Cells
  • Cerebral Cortex / embryology
  • Cerebral Cortex / metabolism
  • Chlorocebus aethiops
  • Ephrin-A5 / genetics
  • Ephrin-A5 / metabolism
  • Gene Expression Regulation, Developmental
  • Growth Cones / physiology*
  • Mice
  • Mice, Transgenic
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Netrin-1
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Semaphorin-3A / genetics
  • Semaphorin-3A / metabolism
  • Thalamus / embryology*
  • Thalamus / physiology*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • beta-Galactosidase / genetics
  • beta-Galactosidase / metabolism

Substances

  • Ephrin-A5
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Ntn1 protein, mouse
  • Receptors, Immunologic
  • Robo2 protein, mouse
  • Sema3a protein, mouse
  • Semaphorin-3A
  • Slit1 protein, mouse
  • Tumor Suppressor Proteins
  • roundabout protein
  • Netrin-1
  • beta-Galactosidase