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

• Published in: PloS one 2017-09, Vol.12 (9), p.e0184767-e0184767
• Main Authors: Blanco, María José, Rodríguez-Martín, Iván, Learte, Ana I R, Clemente, Cristina, Montalvo, María Gregoria, Seiki, Motoharu, Arroyo, Alicia G, Sánchez-Camacho, Cristina
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Aorta; Biology and Life Sciences; Brain; Brain research; Cancer; Catalysis; Cell surface; Cerebral cortex; Cortex (olfactory); Developmental stages; Embryo, Mammalian - metabolism; Embryo, Mammalian - pathology; Embryogenesis; Embryonic Development - genetics; Embryonic growth stage; Endothelium; Enzymes; Extracellular matrix; Eye; Eye lens; Floor plate; Gene Expression Regulation, Developmental; Genes, Reporter; Glycosylphosphatidylinositol; Graduate studies; Immunohistochemistry; Limb buds; Low density lipoprotein receptors; Matrix metalloproteinase; Matrix Metalloproteinase 17 - genetics; Matrix Metalloproteinase 17 - metabolism; Matrix metalloproteinases; Medicine and Health Sciences; Metastases; Mice; Mice, Knockout; Mice, Transgenic; Neostriatum; Nervous system; Neural crest; Notochord; Olfactory bulb; Polymerase chain reaction; Real-Time Polymerase Chain Reaction; Retina; Rodents; Septum; Spinal cord; Studies; Substrates; Tendons; Thalamus; Tissues; Transgenic mice
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0184767

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.