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Publication : Identification of MMP-2 as a novel enhancer of cerebellar granule cell proliferation.

First Author  Verslegers M Year  2013
Journal  Mol Cell Neurosci Volume  57
Pages  63-72 PubMed ID  24141049
Mgi Jnum  J:215734 Mgi Id  MGI:5606152
Doi  10.1016/j.mcn.2013.10.001 Citation  Verslegers M, et al. (2013) Identification of MMP-2 as a novel enhancer of cerebellar granule cell proliferation. Mol Cell Neurosci 57:63-72
abstractText  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.
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