alpha6beta1 integrin directs migration of neuronal precursors in adult mouse forebrain.
New neuroblasts are constantly generated in the adult mammalian subventricular zone (SVZ) and migrate via the very-restricted rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into functional neurons. Several facilitating and repulsive molecules for this migration have been identified, but little is known about chemoattractive molecules involved in the directed nature of this migration in vivo. Here, we investigated the role of the alpha6beta1 integrin, and its ligand, laminin, in controlling guidance of the migrating neuroblasts in adult mice. Immunostaining for the alpha6beta1 integrin was present in neuroblasts and their processes in the anterior/rostral SVZ and the RMS. Inhibition of the endogenous alpha6 or beta1 subunit with locally injected antibodies disrupted the cohesive nature of the RMS, but did not kill the neuroblasts. Infusion of a 15 a.a. peptide, representing the E8 domain of the laminin alpha chains that bind alpha6beta1 integrin, into the neostriatum redirected the neuroblasts away from the RMS towards the site of infusion. Injection of a narrow tract of intact laminin also drew the neuroblasts away from the RMS, but in a more restricted localization. These results suggest a critical role for integrins and laminins in adult SVZ-derived neuroblast migration. They also suggest that integrin-based strategies could be used to direct or restrict neuroblasts to CNS regions where they are needed for cell replacement therapies in the nervous system.
Emsley
J G
JG
Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia, Canada.
Hagg
T
T
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D039121:Integrin alpha6beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007797:Laminin / Q000494:pharmacology; D020547:Lateral Ventricles / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000166:cytology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D016548:Prosencephalon / Q000166:cytology*; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D000906:Antibodies; D039121:Integrin alpha6beta1; D007797:Laminin; D010446:Peptide Fragments; D021122:Protein Subunits