GDNF is a chemoattractant factor for neuronal precursor cells in the rostral migratory stream

Mol Cell Neurosci. 2006 Mar;31(3):505-14. doi: 10.1016/j.mcn.2005.11.007. Epub 2005 Dec 27.


Olfactory bulb (OB) interneurons are generated from neuroblast cells derived from the anterior subventricular zone (SVZa) of the forebrain. The mechanisms guiding the rostral migration of these neuronal precursors are not well understood. Here, we show that glial cell line-derived neurotrophic factor (GDNF) is produced in the olfactory bulb but distributed along the rostral migratory stream (RMS) in a pattern concordant with the expression of its GPI-anchored receptor GFRalpha1. We demonstrate that GDNF is a chemoattractant factor for RMS-derived neuronal precursors, but not for SVZa neuroblast cells. In agreement with this, GDNF increased Cyclin-dependent kinase 5 (Cdk5) activity in RMS cells, a kinase critically involved in neuronal migration and guidance. GDNF-mediated cell chemoattraction was abrogated in RMS explants treated with the Cdk5 inhibitor Roscovitine as well as in RMS explants isolated from Ncam mutant mice. Chemical cross-linking assays showed that 125I-GDNF is able to interact directly with NCAM in RMS-derived cells. Taken together, these data demonstrate that GDNF is a direct chemoattractant factor for neuroblast cells migrating along the RMS and support the participation of NCAM during this guidance process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • CD56 Antigen / genetics
  • CD56 Antigen / metabolism
  • Cells, Cultured
  • Chemotactic Factors / metabolism*
  • Chemotaxis / physiology*
  • Cyclin-Dependent Kinase 5 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 5 / metabolism
  • Enzyme Inhibitors / pharmacology
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism*
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / metabolism
  • Mice
  • Mice, Knockout
  • Neurons / cytology
  • Neurons / metabolism*
  • Olfactory Bulb / cytology
  • Olfactory Bulb / embryology*
  • Olfactory Bulb / growth & development
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Telencephalon / cytology
  • Telencephalon / embryology
  • Telencephalon / growth & development
  • Up-Regulation / physiology


  • CD56 Antigen
  • Chemotactic Factors
  • Enzyme Inhibitors
  • Gfra1 protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Ncam1 protein, mouse
  • Cyclin-Dependent Kinase 5
  • Cdk5 protein, mouse