GDNF is a chemoattractant factor for neuronal precursor cells in the rostral migratory stream.
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.
Paratcha
Gustavo
G
Division of Molecular Neurobiology, Department of Neuroscience, Karolinska Institute, S-17 177 Stockholm, Sweden. gustavo.paratcha@neuro.ki.se
Ibáñez
Carlos F
CF
Ledda
Fernanda
F
D000818:Animals; D000831:Animals, Newborn; D019002:CD56 Antigen / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D015854:Up-Regulation / Q000502:physiology
D019002:CD56 Antigen; D002630:Chemotactic Factors; D004791:Enzyme Inhibitors; C494988:Gfra1 protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; C501063:Ncam1 protein, mouse; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse