Abstract
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 α6β1 integrin, and its ligand, laminin, in controlling guidance of the migrating neuroblasts in adult mice. Immunostaining for the α6β1 integrin was present in neuroblasts and their processes in the anterior/rostral SVZ and the RMS. Inhibition of the endogenous α6 or β1 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 α chains that bind α6β1 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.
Original language | English |
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Pages (from-to) | 273-285 |
Number of pages | 13 |
Journal | Experimental Neurology |
Volume | 183 |
Issue number | 2 |
DOIs | |
Publication status | Published - Oct 1 2003 |
Bibliographical note
Funding Information:We are grateful for the excellent technical assistance of Jessica Pastorius, Teena Chase, Xin Lu, and Min Huang. We are very thankful for the gift of some of the antibodies by Carol Birmingham from Chemicon International Inc. The monoclonal antibody 5A5 anti-PSA-NCAM was raised from a cell line originally developed by Dr. Thomas Jessell, and provided via the Developmental Studies Hybridoma Bank maintained by the University of Iowa. We thank Drs. Wolfram Tetzlaff (UBC) and Eileen Denovan-Wright (Dalhousie) for very helpful discussions. This work was supported by an operating grant (RO14547) from the Canadian Institutes for Health Research in partnership with Nova Neuron Inc., by a Fellowship from the Nova Scotia Health Research Foundation (J.G.E.) and by a CIHR Investigator Award (T.H.).
ASJC Scopus Subject Areas
- Neurology
- Developmental Neuroscience