Developmental expression of membrane type 4-matrix metalloproteinase (Mt4-mmp/Mmp17) in the mouse embryo

PLoS One. 2017 Sep 19;12(9):e0184767. doi: 10.1371/journal.pone.0184767. eCollection 2017.

Abstract

Matrix metalloproteinases (MMPs) constitute a large group of endoproteases that play important functions during embryonic development, tumor metastasis and angiogenesis by degrading components of the extracellular matrix. Within this family, we focused our study on Mt4-mmp (also called Mmp17) that belongs to a distinct subset that is anchored to the cell surface via a glycosylphosphatidylinositol (GPI) moiety and with the catalytic site exposed to the extracellular space. Information about its function and substrates is very limited to date, and little has been reported on its role in the developing embryo. Here, we report a detailed expression analysis of Mt4-mmp during mouse embryonic development by using a LacZ reporter transgenic mouse line. We showed that Mt4-mmp is detected from early stages of development to postnatal stages following a dynamic and restricted pattern of expression. Mt4-mmp was first detected at E8.5 limited to the intersomitic vascularization, the endocardial endothelium and the dorsal aorta. Mt4-mmpLacZ/+ cells were also observed in the neural crest cells, somites, floor plate and notochord at early stages. From E10.5, expression localized in the limb buds and persists during limb development. A strong expression in the brain begins at E12.5 and continues to postnatal stages. Specifically, staining was observed in the olfactory bulb, cerebral cortex, hippocampus, striatum, septum, dorsal thalamus and the spinal cord. In addition, LacZ-positive cells were also detected during eye development, initially at the hyaloid artery and later on located in the lens and the neural retina. Mt4-mmp expression was confirmed by quantitative RT-PCR and western blot analysis in some embryonic tissues. Our data point to distinct functions for this metalloproteinase during embryonic development, particularly during brain formation, angiogenesis and limb development.

MeSH terms

  • Animals
  • Embryo, Mammalian / metabolism*
  • Embryo, Mammalian / pathology
  • Embryonic Development / genetics
  • Gene Expression Regulation, Developmental
  • Genes, Reporter
  • Immunohistochemistry
  • Matrix Metalloproteinase 17 / genetics
  • Matrix Metalloproteinase 17 / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Real-Time Polymerase Chain Reaction

Substances

  • Matrix Metalloproteinase 17

Grants and funding

This work was supported by a grant from the Universidad Europea de Madrid (2016UEM04) to C.S.C. and grant SAF2014-20520R from the Ministry of Economy, Industry and Competitiveness (MIEC) to A.G.A. The CNIC is supported by the MIEC and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).