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Neural MMP-28 expression precedes myelination during development and peripheral nerve repair
Sean R Werner1, Anthony L Mescher, Anton W Neff
1Biotherapeutic Discovery Research, Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, Indiana 46225, USA. wernerse@lilly.com
Abstract:
Mammalian matrix metalloproteinase 28 (MMP-28) is expressed in several normal adult tissues, and during cutaneous wound healing. We show that, in frog and mouse embryos, MMP-28 is expressed predominantly throughout the nervous system. Xenopus expression increases during neurulation and remains elevated through early limb development where it is expressed in nerves. In the mouse, neural expression peaks at embryonic day (E) 14 but remains detectable through E17. During frog hindlimb regeneration XMMP-28 is not initially expressed in the regenerating nerves but is detectable before myelination. Following hindlimb denervation, XMMP-28 expression is detectable along regenerating nerves before myelination. In embryonic rat neuron-glial co-cultures, MMP-28 decreases after the initiation of myelination. Incubation of embryonic brain tissue with purified MMP-28 leads to the degradation of multiple myelin proteins. These results suggest that MMP-28 plays an evolutionarily conserved role in neural development and is likely to modulate the axonal-glial extracellular microenvironment.
Insights
Matrix metalloproteinase 28 (MMP-28) is crucial for neural development in frogs and mice. This protein regulates the nerve microenvironment by affecting myelin proteins during development and regeneration.
Area of Science:
- Neuroscience
- Developmental Biology
- Biochemistry
Background:
- Matrix metalloproteinase 28 (MMP-28) is known for its roles in adult tissues and wound healing.
- Its function in the developing nervous system is largely unexplored.
Purpose of the Study:
- To investigate the expression pattern and functional role of MMP-28 in the developing and regenerating nervous system.
- To determine MMP-28's potential involvement in myelination and neural microenvironment modulation.
Main Methods:
- Expression analysis of MMP-28 in Xenopus and mouse embryos during development.
- Analysis of MMP-28 expression during hindlimb regeneration and after denervation in Xenopus.
- In vitro studies using rat neuron-glial co-cultures to assess MMP-28's effect on myelination.
- Biochemical assays to evaluate MMP-28's impact on myelin proteins.
Main Results:
- MMP-28 is predominantly expressed in the nervous system of frog and mouse embryos, with expression peaking during neurulation and early limb development.
- In Xenopus, XMMP-28 is detected in regenerating nerves before myelination and after denervation.
- MMP-28 levels decrease post-myelination initiation in rat neuron-glial cultures.
- Purified MMP-28 degrades key myelin proteins in embryonic brain tissue.
Conclusions:
- MMP-28 plays an evolutionarily conserved role in neural development.
- MMP-28 likely modulates the axonal-glial extracellular microenvironment, potentially regulating myelination processes.
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