MMP-9 deficiency affects axonal outgrowth, migration, and apoptosis in the developing cerebellum
| Autor: | Marie-Françoise Belin, Leif R. Lund, Claire Meissirel, Catherine Vaillant, Nicole Thomasset, Mireille Mutin |
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| Přispěvatelé: | Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2003 |
| Předmět: |
Cerebellum
Programmed cell death [SDV]Life Sciences [q-bio] Morphogenesis Apoptosis Matrix metalloproteinase Biology Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Cell Movement medicine Extracellular Animals Molecular Biology ComputingMilieux_MISCELLANEOUS 030304 developmental biology Mice Knockout 0303 health sciences Cell migration Cell Biology Granule cell Axons Cell biology Mice Inbred C57BL medicine.anatomical_structure CXCL3 Animals Newborn Matrix Metalloproteinase 9 Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Molecular and Cellular Neuroscience Molecular and Cellular Neuroscience, Elsevier, 2003, 24 (2), pp.395-408. ⟨10.1016/s1044-7431(03)00196-9⟩ |
| ISSN: | 1044-7431 1095-9327 |
| Popis: | Matrix metalloproteinases (MMPs) are responsible for the extensive extracellular proteolysis that plays a central role in regulating the pericellular environment, contributing to morphogenesis and developmental remodeling. In the CNS, there is increasing in vitro evidence for the involvement of MMPs in neurite elongation and axonal guidance. Here, we show that expression of MMP-9 is spatiotemporally related to cerebellar granule cell migration during postnatal development. Using cerebellar explant cultures, we demonstrated that a specific MMP-9-blocking antibody affects granular cell axonal outgrowth and migration in a dose-dependent manner. In addition, the in vivo analysis of MMP-9-deficient mice revealed abnormal accumulation of granular precursors (GPs) in the external granular layer (EGL) at a time when migration is normally extensive. Furthermore, GP migration was delayed and their programmed cell death was reduced in MMP-9-deficient mice, suggesting that MMP-9 is involved in the control of granule cell migration and apoptosis. These results provide direct evidence for a physiological role of MMP-9 in neuronal precursor migration and apoptosis in the developing cerebellum, and emphasize the importance of MMP-9 in the temporal regulation of the cerebellar microenvironment. |
| Databáze: | OpenAIRE |
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