title: Membrane-type MMPs are indispensable for placental labyrinth formation and development.
abstract: The membrane-type matrix metalloproteinases (MT-MMPs) are essential for pericellular matrix remodeling in late stages of development, as well as in growth and tissue homeostasis in postnatal life. Although early morphogenesis is perceived to involve substantial tissue remodeling, the roles of MT-MMPs in these processes are only partially characterized. Here we explore the functions of 2 prominently expressed MT-MMPs, MT1-MMP and MT2-MMP, and describe their roles in the process of placental morphogenesis. The fetal portion of the placenta, in particular the labyrinth (LA), displays strong overlapping expression of MT1-MMP and MT2-MMP, which is critical for syncytiotrophoblast formation and in turn for fetal vessels. Disruption of trophoblast syncytium formation consequently leads to developmental arrest with only a few poorly branched fetal vessels entering the LA causing embryonic death at embryonic day 11.5. Through knockdown of MMP expression, we demonstrate that either MT1-MMP or MT2-MMP is crucial specifically during development of the LA. In contrast, knockdown of MT-MMP activity after LA formation is compatible with development to term and postnatal life. Taken together these data identify essential but interchangeable roles for MT1-MMP or MT2-MMP in placental vasculogenesis and provide the first example of selective temporal and spatial MMP activity required for development of the mouse embryo.
authors.affiliation: Craniofacial and Skeletal Diseases Branch, National Institute of Dental andCraniofacial Research, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Szabova
authors.forename: Mee-Young
authors.initials: MY
authors.lastname: Son
authors.forename: Joanne
authors.initials: J
authors.lastname: Shi
authors.forename: Marek
authors.initials: M
authors.lastname: Sramko
authors.forename: Susan S
authors.initials: SS
authors.lastname: Yamada
authors.forename: William D
authors.initials: WD
authors.lastname: Swaim
authors.forename: Patricia
authors.initials: P
authors.lastname: Zerfas
authors.forename: Stacie
authors.initials: S
authors.lastname: Kahan
authors.forename: Kenn
authors.initials: K
authors.lastname: Holmbeck
mesh_terms: D000818:Animals; D015153:Blotting, Western; D007758:Ear, Inner / Q000196:embryology* / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D007124:Immunoenzyme Techniques; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*; D053517:Matrix Metalloproteinase 15 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010920:Placenta / Q000196:embryology* / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D011270:Pregnancy, Animal
chemical_list: C507096:Mmp14 protein, mouse; C507100:Mmp15 protein, mouse; D053517:Matrix Metalloproteinase 15; D053511:Matrix Metalloproteinase 14