caa a22 4500 606202226 CHVBK 20210128100952.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s00429-014-0747-3 doi (NATIONALLICENCE)springer-10.1007/s00429-014-0747-3 MMP-2 mediates Purkinje cell morphogenesis and spine development in the mouse cerebellum [Elektronische Daten] [Mieke Verslegers, Inge Van Hove, Eline Dekeyster, Ilse Gantois, Tjing-Tjing Hu, Rudi D'Hooge, Lutgarde Arckens, Lieve Moons] Matrix metalloproteinase-2 (MMP-2) is a highly studied proteolytic enzyme, involved in many detrimental and beneficial functions throughout the body, and also active in the central nervous system (CNS). MMP-2 is profoundly expressed in the developing cerebellum and was recently reported to modulate granule cell proliferation by affecting cell cycle kinetics in cerebella of postnatal day 3 mouse pups. In this report, a two-dimensional difference gel electrophoresis proteomics study was implemented at this postnatal stage and revealed 16 differentially expressed proteins between MMP-2-deficient (MMP-2−/−) and wild-type cerebella. Among those, collapsin response mediator protein 1 (CRMP1) could be identified as the most significant differential protein between the two genotypes. Western blot experiments confirmed this finding and further disclosed a significant increase in phosphorylated CRMP1 expression in MMP-2−/− cerebella. Strikingly, subsequent immunohistochemical and microscopic analyses revealed an aberrant Purkinje cell (PC) dendritogenesis, possibly related to upregulated (phospho-) CRMP1 levels in these neonatal MMP-2−/− animals. Further, detailed morphometric analyses showed persistent PC morphological changes in MMP-2−/− mice, from the neonatal stage until adulthood. These were characterized by a reduced growth of PC somata, reduced dendritic tree sizes, and a decreased dendritic arborization. During development, the observed defects were accompanied by a temporarily disturbed parallel fiber and climbing fiber synaptic input on the PCs, while in adult MMP-2−/− animals, an increased PC spine density and reduced spine lengths were noted. The observed PC abnormalities might contribute to the milddefects in motor performance, i.e. balance and coordination, detected in adult MMP-2−/− mice. Overall, these findings indicate the importance of MMP-2 in CNS development and dendritogenesis, and highlight the importance of a correct developmental wiring for adult brain morphology and function. Springer-Verlag Berlin Heidelberg, 2014 Cerebellum nationallicence Purkinje cell nationallicence Matrix metalloproteinase-2 nationallicence Neuronal patterning nationallicence Synaptogenesis nationallicence Motor behavior nationallicence Verslegers Mieke Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium aut Van Hove Inge Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium aut Dekeyster Eline Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium aut Gantois Ilse Laboratory of Biological Psychology, Department of Psychology, KU Leuven, Leuven, Belgium aut Hu Tjing-Tjing Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium aut D'Hooge Rudi Laboratory of Biological Psychology, Department of Psychology, KU Leuven, Leuven, Belgium aut Arckens Lutgarde Laboratory of Neuroplasticity and Neuroproteomics, Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium aut Moons Lieve Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium aut Brain Structure and Function Springer Berlin Heidelberg 220/3(2015-05-01), 1601-1617 1863-2653 220:3<1601 2015 220 429 https://doi.org/10.1007/s00429-014-0747-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0747-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Verslegers Mieke Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium aut NATIONALLICENCE 700 1- Van Hove Inge Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium aut NATIONALLICENCE 700 1- Dekeyster Eline Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium aut NATIONALLICENCE 700 1- Gantois Ilse Laboratory of Biological Psychology, Department of Psychology, KU Leuven, Leuven, Belgium aut NATIONALLICENCE 700 1- Hu Tjing-Tjing Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium aut NATIONALLICENCE 700 1- D'Hooge Rudi Laboratory of Biological Psychology, Department of Psychology, KU Leuven, Leuven, Belgium aut NATIONALLICENCE 700 1- Arckens Lutgarde Laboratory of Neuroplasticity and Neuroproteomics, Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium aut NATIONALLICENCE 700 1- Moons Lieve Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/3(2015-05-01), 1601-1617 1863-2653 220:3<1601 2015 220 429