Netrin1 exerts a chemorepulsive effect on migrating cerebellar interneurons in a Dcc-independent way

Mol Cell Neurosci. 2006 Dec;33(4):389-400. doi: 10.1016/j.mcn.2006.08.010. Epub 2006 Oct 9.

Abstract

Few studies have addressed the issue of how GABAergic interneurons in the cerebellar cortex migrate or what guidance cues steer them. Recent data show that their development starts at the cerebellar germinal epithelium on top of the fourth ventricle. These interneurons continue to proliferate in the postnatal cerebellar white matter and later migrate to their final position in the cerebellar cortex. Here we report the chemorepulsive action of Netrin1 on postnatal cerebellar interneurons in vitro and also show the expression pattern of Netrin1 and its receptors Dcc and Unc5. Our expression results further suggest that Netrin1 is involved in the migration of GABAergic interneurons in vivo. Moreover, our data point to Bergmann glial fibers as possible tracks for these cells en route to the molecular layer. Finally, experiments using blocking antibodies allow us to conclude that Dcc, although expressed by postnatal cerebellar interneurons, is not involved in the repulsive response triggered by Netrin1 in these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Cell Count / methods
  • Cell Movement / drug effects*
  • Cell Movement / physiology
  • Cerebellum / cytology*
  • DCC Receptor
  • Drug Interactions
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / physiology
  • Glial Fibrillary Acidic Protein / metabolism
  • Green Fluorescent Proteins / metabolism
  • Immunohistochemistry / methods
  • In Situ Hybridization / methods
  • Interneurons / drug effects*
  • Interneurons / physiology
  • Mice
  • Mice, Transgenic
  • Nerve Growth Factors / pharmacology*
  • Netrin-1
  • Organ Culture Techniques
  • PAX2 Transcription Factor / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptors, Cell Surface / physiology*
  • Tumor Suppressor Proteins / pharmacology*
  • Tumor Suppressor Proteins / physiology*
  • gamma-Aminobutyric Acid / metabolism

Substances

  • DCC Receptor
  • Dcc protein, mouse
  • Glial Fibrillary Acidic Protein
  • Nerve Growth Factors
  • PAX2 Transcription Factor
  • Receptors, Cell Surface
  • Tumor Suppressor Proteins
  • Green Fluorescent Proteins
  • Netrin-1
  • gamma-Aminobutyric Acid
  • Protein-Serine-Threonine Kinases