S20-04 Mechanisms of neuronal migration in the developing cerebral cortex

in NCC. Detailed analysis of one protease, the gelatinase MMP9, confirmed its distribution in cranial and trunk NCC. Exogenous MMP9 resulted in enhanced and precocious delamination of NCC, evident by Foxd3 or HNK1 staining. Conversely, prevention of MMP9 production or activation, using morpholino oligonucleotides or a pharmacological inhibitor, respectively, revealed a dramatic inhibition in NCC migration, without perturbing their specification or survival. The effect of MMP9 was shown to be mediated by reduction of N-cadherin and disruption in stress fibers, suggesting that MMP9 executes NCC migration by breaking cell–cell interactions and altering cytoskeleton organization. Taken together, this study shows for the first time the critical role of MMP9 in promoting the switch from epithelial to motile NCC.