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Tissue-Specific Stem Cells
Article first published online: 24 FEB 2011
Copyright © 2010 AlphaMed Press
Volume 29, Issue 2, pages 332–343, February 2011
How to Cite
Leong, S. Y., Faux, C. H., Turbic, A., Dixon, K. J. and Turnley, A. M. (2011), The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration. STEM CELLS, 29: 332–343. doi: 10.1002/stem.577
Author contributions: S.Y.L.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; C.H.F. and A.T.: collection and assembly of data, data analysis and interpretation; K.J.D.: collection of data; A.M.T.: conception and design, financial support, data analysis and interpretation, manuscript writing, final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS December 9, 2010.
- Issue published online: 24 FEB 2011
- Article first published online: 24 FEB 2011
- Accepted manuscript online: 9 DEC 2010 08:27AM EST
- Manuscript Accepted: 19 NOV 2010
- Manuscript Received: 2 FEB 2010
- National Health and Medical Research Council of Australia Project grant. Grant Numbers: 454384, 350226
- Rho-dependent kinase;
- Subventricular zone;
- Neural stem cell;
- Rostral migratory stream;
Adult neural precursor cells (NPCs) in the subventricular zone (SVZ) normally migrate via the rostral migratory stream (RMS) to the olfactory bulb (OB). Following neural injury, they also migrate to the site of damage. This study investigated the role of Rho-dependent kinase (ROCK) on the migration of NPCs in vitro and in vivo. In vitro, using neurospheres or SVZ explants, inhibition of ROCK using Y27632 promoted cell body elongation, process protrusion, and migration, while inhibiting NPC chain formation. It had no effect on proliferation, apoptosis, or differentiation. Both isoforms of ROCK were involved. Using siRNA, knockdown of both ROCK1 and ROCK2 was required to promote NPC migration and morphological changes; knockdown of ROCK2 alone was partially effective, with little/no effect of knockdown of ROCK1 alone. In vivo, infusion of Y27632 plus Bromodeoxyuridine (BrdU) into the lateral ventricle for 1 week reduced the number of BrdU-labeled NPCs in the OB compared with BrdU infusion alone. However, ROCK inhibition did not affect the tangential-to-radial switch of NPC migration, as labeled cells were present in all OB layers. The decrease in NPC number at the OB was not attributed to a decrease in NPCs at the SVZ. However, ROCK inhibition decreased the density of BrdU-labeled cells in the RMS and increased the distribution of these cells to ectopic brain regions, such as the accessory olfactory nucleus, where the majority differentiated into neurons. These findings suggest that ROCK signaling regulates NPC migration via regulation of cell-cell contact and chain migration. STEM CELLS 2011;29:332–343