Molecular Neurobiology

, Volume 45, Issue 1, pp 17–29

An Aberrant Cerebellar Development in Mice Lacking Matrix Metalloproteinase-3

  • Inge Van Hove
  • Mieke Verslegers
  • Tom Buyens
  • Nathalie Delorme
  • Kim Lemmens
  • Stijn Stroobants
  • Ilse Gantois
  • Rudi D’Hooge
  • Lieve Moons
Article

DOI: 10.1007/s12035-011-8215-z

Cite this article as:
Van Hove, I., Verslegers, M., Buyens, T. et al. Mol Neurobiol (2012) 45: 17. doi:10.1007/s12035-011-8215-z

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.

Keywords

Matrix metalloproteinase-3DevelopmentCerebellumNeuronal patterningPurkinje cell dendritogenesisNeuronal wiring

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Inge Van Hove
    • 1
  • Mieke Verslegers
    • 1
  • Tom Buyens
    • 1
  • Nathalie Delorme
    • 1
  • Kim Lemmens
    • 1
  • Stijn Stroobants
    • 2
  • Ilse Gantois
    • 2
  • Rudi D’Hooge
    • 2
  • Lieve Moons
    • 1
  1. 1.Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of BiologyK.U.LeuvenLeuvenBelgium
  2. 2.Laboratory of Biological Psychology, Department of PsychologyK.U.LeuvenLeuvenBelgium