title: An aberrant cerebellar development in mice lacking matrix metalloproteinase-3.
abstract: Cell-cell and cell-matrix interactions are necessary for neuronal patterning and brain wiring during development. Matrix metalloproteinases (MMPs) are proteolytic enzymes capable of remodelling the pericellular environment and regulating signaling pathways through cleavage of a large degradome. MMPs have been suggested to affect cerebellar development, but the specific role of different MMPs in cerebellar morphogenesis remains unclear. Here, we report a role for MMP-3 in the histogenesis of the mouse cerebellar cortex. MMP-3 expression peaks during the second week of postnatal cerebellar development and is most prominently observed in Purkinje cells (PCs). In MMP-3 deficient (MMP-3(-/-)) mice, a protracted granule cell (GC) tangential migration and a delayed GC radial migration results in a thicker and persistent external granular layer, a retarded arrival of GCs in the inner granular layer, and a delayed GABAergic interneuron migration. Importantly, these neuronal migration anomalies, as well as the consequent disturbed synaptogenesis on PCs, seem to be caused by an abnormal PC dendritogenesis, which results in reduced PC dendritic trees in the adult cerebellum. Of note, these developmental and adult cerebellar defects might contribute to the aberrant motor phenotype observed in MMP-3(-/-) mice and suggest an involvement of MMP-3 in mouse cerebellar development.
authors: Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology, K.U.Leuven, Naamsestraat 61, Box 2464, 3000 Leuven, Belgium.
authors: Inge
authors: I
authors: Van Hove
authors: Mieke
authors: M
authors: Verslegers
authors: Tom
authors: T
authors: Buyens
authors: Nathalie
authors: N
authors: Delorme
authors: Kim
authors: K
authors: Lemmens
authors: Stijn
authors: S
authors: Stroobants
authors: Ilse
authors: I
authors: Gantois
authors: Rudi
authors: R
authors: D'Hooge
authors: Lieve
authors: L
authors: Moons
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019521:Body Patterning / Q000235:genetics; D002531:Cerebellum / Q000002:abnormalities* / Q000254:growth & development / Q000503:physiopathology; D004195:Disease Models, Animal; D019278:Matrix Metalloproteinase 3 / Q000172:deficiency* / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009421:Nervous System Malformations / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype
chemical_list: D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse