Journal article
Developmental expression of matrix metalloproteinases 2 and 9 and their potential role in the histogenesis of the cerebellar cortex
Journal of comparative neurology (1911), Vol.481(4), pp.403-415
01/24/2005
DOI: 10.1002/cne.20375
PMID: 15593342
Abstract
The development of the cerebellar cortex depends on intrinsic genetic programs and orchestrated cell-cell/cell-matrix interactions. Matrix metalloproteinases (MMPs) are proteolytic enzymes that play an important role in these interactions. MMP-2 and MMP-9 are involved in diverse neuronal functions including migration, process extension, and synaptic plasticity. We investigated the spatiotemporal pattern of expression/activity of MMP-2/MMP-9 in the developing cerebellum and their role in the histogenesis of the cerebellar cortex. The levels of transcripts of MMP-2/MMP-9 were measured with real-time quantitative polymerase chain reaction. An initial decrease in MMP-2/MMP-9 transcripts was observed between postnatal days 3 (PD3) and PD6, and the mRNA levels remained relatively constant thereafter. Zymographic analysis revealed that the expression/activity of MMP-2/MMP-9 persisted longer than their transcripts; the downregulation occurred around PD9, suggesting a mechanism of translational or post-translational regulation. The gelatinase activity was localized in the external granule layer (EGL) and the internal granule layer during PD3-PD12. The immunoreactivity of MMP-2 was mainly localized in the EGL, the Bergmann glial fibers, and the Purkinje cell layer (PCL), whereas MMP-9 immunoreactivity was detected intensively in the PCL and the extracellular space of the molecular layer. Expression of MMP-9 was relatively weak in the EGL. The immunoreactivity of MMP-2/MMP-9 became undetectable after PD21. A similar expression pattern of MMP-2/MMP-9 was observed in organotypic cerebellar slice cultures. Exposure of organotypic slices to a specific MMP-2/MMP-9 inhibitor significantly increased the thickness of the EGL and concurrently decreased the number of migrating granule neurons in the molecular layer. Thus, MMP-2 and MMP-9 play a role in the postnatal cerebellar morphogenesis.
Details
- Title: Subtitle
- Developmental expression of matrix metalloproteinases 2 and 9 and their potential role in the histogenesis of the cerebellar cortex
- Creators
- Albert E Ayoub - West Virginia UniversityTian-Quan Cai - Department of Atherosclerosis and Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065Rebecca A Kaplan - Merck & Co.Jia Luo - West Virginia University
- Resource Type
- Journal article
- Publication Details
- Journal of comparative neurology (1911), Vol.481(4), pp.403-415
- Publisher
- Wiley Subscription Services, Inc., A Wiley Company
- DOI
- 10.1002/cne.20375
- PMID
- 15593342
- ISSN
- 0021-9967
- eISSN
- 1096-9861
- Number of pages
- 13
- Language
- English
- Date published
- 01/24/2005
- Academic Unit
- Pathology
- Record Identifier
- 9984186659802771
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