Abstract
Olfactory ensheathing cells (OECs) migrate from the olfactory epithelium towards the olfactory bulb during development. However, the guidance mechanism for OEC migration remains a mystery. Here we show that migrating OECs expressed the receptor of the repulsive guidance factor Slit-2. A gradient of Slit-2 in front of cultured OECs first caused the collapse of the leading front, then the reversal of cell migration. These Slit-2 effects depended on the Ca2+ release from internal stores through inositol (1,4,5)-triphosphate receptor channels. Interestingly, in response to Slit-2 stimulation, collapse of the leading front required the activation of the F-actin severing protein cofilin in a Ca2+-dependent manner, whereas the subsequent reversal of the soma migration depended on the reversal of RhoA activity across the cell. Finally, the Slit-2-induced repulsion of cell migration was fully mimicked by co-application of inhibitors of F-actin polymerization and RhoA kinase. Our findings revealed Slit-2 as a repulsive guidance factor for OEC migration and an unexpected link between Ca2+ and cofilin signaling during Slit-2-triggered repulsion.
Original language | English (US) |
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Pages (from-to) | 186-197 |
Number of pages | 12 |
Journal | Journal of Cell Science |
Volume | 124 |
Issue number | 2 |
DOIs | |
State | Published - Jan 15 2011 |
Keywords
- Ca
- Cofilin
- Migration
- Olfactory ensheathing cells
- RhoA
- Slit-2
ASJC Scopus subject areas
- Cell Biology