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The Rho Kinase Pathway Regulates Mouse Adult Neural Precursor Cell Migration.
MedLine Citation:
PMID:  21154557     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Adult neural precursor cells (NPCs) in the subventricular zone (SVZ) normally migrate via the rostral migratory stream 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 BrdU into the lateral ventricle for 1 week reduced the number of BrdU labeled NPCs in the OB compared to 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 rostral migratory stream 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.
Authors:
Soo Yuen Leong; Clare Helen Faux; Alisa Turbic; Kirsty Jane Dixon; Ann Maree Turnley
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-12-9
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  -     ISSN:  1549-4918     ISO Abbreviation:  -     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Centre for Neuroscience, The University of Melbourne, Victoria, 3010, Australia.
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