Slit antagonizes netrin-1 attractive effects during the migration of inferior olivary neurons

Dev Biol. 2002 Jun 15;246(2):429-40. doi: 10.1006/dbio.2002.0681.

Abstract

Inferior olivary neurons (ION) migrate circumferentially around the caudal rhombencephalon starting from the alar plate to locate ventrally close to the floor-plate, ipsilaterally to their site of proliferation. The floor-plate constitutes a source of diffusible factors. Among them, netrin-1 is implied in the survival and attraction of migrating ION in vivo and in vitro. We have looked for a possible involvement of slit-1/2 during ION migration. We report that: (1) slit-1 and slit-2 are coexpressed in the floor-plate of the rhombencephalon throughout ION development; (2) robo-2, a slit receptor, is expressed in migrating ION, in particular when they reach the vicinity of the floor-plate; (3) using in vitro assays in collagen matrix, netrin-1 exerts an attractive effect on ION leading processes and nuclei; (4) slit has a weak repulsive effect on ION axon outgrowth and no effect on migration by itself, but (5) when combined with netrin-1, it antagonizes part of or all of the effects of netrin-1 in a dose-dependent manner, inhibiting the attraction of axons and the migration of cell nuclei. Our results indicate that slit silences the attractive effects of netrin-1 and could participate in the correct ventral positioning of ION, stopping the migration when cell bodies reach the floor-plate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons
  • Cell Movement*
  • Coculture Techniques
  • In Situ Hybridization
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Nerve Growth Factors / antagonists & inhibitors*
  • Nerve Growth Factors / physiology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Netrin-1
  • Neurons / metabolism*
  • Olivary Nucleus / cytology*
  • Olivary Nucleus / embryology
  • Tumor Suppressor Proteins

Substances

  • Intercellular Signaling Peptides and Proteins
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Ntn1 protein, mouse
  • Slit1 protein, mouse
  • Tumor Suppressor Proteins
  • Netrin-1
  • Slit homolog 2 protein