title: Identification of MMP-2 as a novel enhancer of cerebellar granule cell proliferation.
abstract: During the first postnatal days in the mouse, granule cells (GCs) undergo massive proliferation, which then gradually decreases. Matrix metalloproteinase-2 (MMP-2), a Zn(2+)-dependent proteolytic enzyme, is involved in a wide variety of pathological and physiological pathways. Evidence for a role of this proteinase in cell proliferation is emerging, reporting its involvement in pathological proliferation, as well as during neurogenesis and developmental proliferation of non-CNS tissues. In this study, MMP-2 protein expression was observed within the early postnatal cerebellar cortex, predominantly in Purkinje cells and within the GC proliferative zone, i.e. the superficial external granular layer (EGL). Consistently, the spatiotemporal MMP-2 mRNA and protein profiles highly correlated with the peak of GC precursor (GCP) proliferation and detailed morphometric analyses of MMP-2 deficient cerebella revealed a thinner EGL due to a decreased GCP proliferation. BrdU cumulative experiments, performed to measure the length of different cell cycle phases, further disclosed a transiently prolonged S-phase in MMP-2 deficient GCPs during early cerebellar development. In consequence, MMP-2 deficient animals displayed a transient delay in GC migration towards the IGL. In conclusion, our findings provide important evidence for a role for MMP-2 in neuronal proliferation and cell cycle kinetics in the developing CNS.
authors.affiliation: Laboratory of Neural Circuit Development and Regeneration, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, Leuven, Belgium.
authors.forename: Mieke
authors.initials: M
authors.lastname: Verslegers
authors.forename: Inge
authors.initials: I
authors.lastname: Van Hove
authors.forename: Tom
authors.initials: T
authors.lastname: Buyens
authors.forename: Eline
authors.initials: E
authors.lastname: Dekeyster
authors.forename: Ellen
authors.initials: E
authors.lastname: Knevels
authors.forename: Lieve
authors.initials: L
authors.lastname: Moons
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002531:Cerebellum / Q000166:cytology / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011689:Purkinje Cells / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse
keywords: Cerebellum; Matrix metalloproteinase-2; Neuronal proliferation; Postnatal development