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Cerebral Cortex Advance Access originally published online on October 4, 2006
Cerebral Cortex 2007 17(7):1712-1721; doi:10.1093/cercor/bhl082
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Functional Interaction between Matrix Metalloproteinase-3 and Semaphorin-3C during Cortical Axonal Growth and Guidance

B Gonthier, C Nasarre, L Roth, M Perraut, N Thomasset, G Roussel, D Aunis and D Bagnard

INSERM U575, Physiopathologie du Système Nerveux, Centre de Neurochimie, 67084 Strasbourg, France

Address correspondence to Dr D. Bagnard, INSERM U575, Physiopathologie du Système Nerveux, Centre de Neurochimie, 5 Rue Blaise Pascal, 67084 Strasbourg, France. Email: Dominique.Bagnard{at}inserm.u-strasbg.fr.

In the developing cortex, axons and dendrites extend progressively in response to environmental cues attracting or repelling growing processes. Recent evidence suggests the existence of a functional link between guidance molecules and metalloproteinases. Here, we analyzed the putative functional interaction of matrix metalloproteinases (MMPs) with guidance cues of the semaphorin family during growth and guidance of cortical axons. Our results demonstrate that the expression pattern and the proteolytic activity of MMP-3 are consistent with a role of this particular MMP during cortical axon outgrowth. We found that MMP-3 is required for an optimal axon extension and is involved in the Sema3C-dependent chemoattraction of cortical axons by modulating both the growth capacity and the orientation of growth. Interestingly, the inhibitory Sema3A decreased both the expression and activity of MMP-3. Taken together, our results reveal a molecular interaction between MMPs and semaphorins providing new insight into the molecular mechanism allowing axonal growth cone to respond to environmental guidance cues in the context of cortical development.

Key Words: axon guidance • axon outgrowth • cortex • development • matrix metalloproteinase • semaphorin


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