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Published on: June 26, 2018
Dynamic Expression of Membrane Type 1-Matrix Metalloproteinase (Mt1-mmp/Mmp14) in the Mouse Embryo
Emma Muñoz-Sáez1, Natalia Moracho2, Ana I R Learte3
1Department of Health Science, School of Biomedical Sciences, Universidad Europea de Madrid, 28670 Villaviciosa de Odón, Spain.
Abstract:
MT1-MMP/MMP14 belongs to a subgroup of the matrix metalloproteinases family that presents a transmembrane domain, with a cytosolic tail and the catalytic site exposed to the extracellular space. Deficient mice for this enzyme result in early postnatal death and display severe defects in skeletal, muscle and lung development. By using a transgenic line expressing the LacZ reporter under the control of the endogenous Mt1-mmp promoter, we reported a dynamic spatiotemporal expression pattern for Mt1-mmp from early embryonic to perinatal stages during cardiovascular development and brain formation. Thus, Mt1-mmp shows expression in the endocardium of the heart and the truncus arteriosus by E8.5, and is also strongly detected during vascular system development as well as in endothelial cells. In the brain, LacZ reporter expression was detected in the olfactory bulb, the rostral cerebral cortex and the caudal mesencephalic tectum. LacZ-positive cells were observed in neural progenitors of the spinal cord, neural crest cells and the intersomitic region. In the limb, Mt1-mmp expression was restricted to blood vessels, cartilage primordium and muscles. Detection of the enzyme was confirmed by Western blot and immunohistochemical analysis. We suggest novel functions for this metalloproteinase in angiogenesis, endocardial formation and vascularization during organogenesis. Moreover, Mt1-mmp expression revealed that the enzyme may contribute to heart, muscle and brain throughout development.
Insights
Matrix metalloproteinase 14 (MT1-MMP) plays a crucial role in cardiovascular and brain development. Its dynamic expression pattern suggests novel functions in angiogenesis and organogenesis.
Area of Science:
- Biochemistry
- Developmental Biology
- Molecular Biology
Background:
- Matrix metalloproteinases (MMPs) are enzymes involved in extracellular matrix degradation.
- MT1-MMP (MMP14) is a transmembrane MMP with a unique structure and essential developmental roles.
- Mice deficient in MT1-MMP exhibit severe developmental defects and early postnatal death.
Purpose of the Study:
- To investigate the spatiotemporal expression pattern of MT1-MMP during embryonic and perinatal development.
- To identify novel functions of MT1-MMP in cardiovascular and brain formation.
- To elucidate the role of MT1-MMP in organogenesis.
Main Methods:
- Utilized a transgenic mouse line with a LacZ reporter under the Mt1-mmp promoter.
- Analyzed LacZ expression patterns during various developmental stages (embryonic to perinatal).
- Confirmed enzyme detection using Western blot and immunohistochemical analysis.
Main Results:
- Dynamic MT1-MMP expression observed in the developing cardiovascular system, including endocardium and truncus arteriosus.
- Significant expression detected in brain regions (olfactory bulb, cerebral cortex, mesencephalic tectum) and neural progenitors.
- MT1-MMP localized to blood vessels, cartilage, and muscles in developing limbs.
- Expression confirmed in endothelial cells, neural crest cells, and intersomitic regions.
Conclusions:
- MT1-MMP exhibits dynamic spatiotemporal expression critical for cardiovascular and brain development.
- Suggests novel roles for MT1-MMP in angiogenesis, endocardial formation, and vascularization.
- MT1-MMP is essential for the proper development of the heart, muscles, and brain.
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