Tissue inhibitor of metalloproteinase-2 (TIMP-2) expression during cardiac neural crest cell migration and its role in proMMP-2 activation.
Matrix metalloproteinases (MMPs) are important mediators of neural crest (NC) cell migration. Here, we examine the distribution of tissue inhibitor of metalloproteinase (TIMP) -2 and TIMP-3 and test whether manipulating TIMP levels alters chicken cardiac NC cell migration. TIMP-2 mRNA is expressed at stage 11 in the neural epithelium and only in migrating cardiac NC cells. TIMP-3 mRNA is expressed only in the notochord at stage 8 and later in the outflow tract myocardium. Exogenous TIMP-2 increases NC motility in vitro at low concentrations but has no effect when concentrations are increased. In vitro, NC cells express membrane type-1 matrix metalloproteinase (MT1-MMP) and TIMP-2 and they secrete and activate proMMP-2. Antisense TIMP-2 oligonucleotides block proMMP-2 activation, decrease NC cell migration from explants, and perturb NC morphogenesis in ovo. Because TIMP-2 is required for activation of proMMP-2 by MT1-MMP, this finding suggests TIMP-2 expression by cardiac NC cells initiates proMMP-2 activation important for their migration.
Cantemir
V
V
Department of Biomedical Science, Creighton University, Omaha, Nebraska 68178, USA.
Cai
D H
DH
Reedy
M V
MV
Brauer
P R
PR
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002642:Chick Embryo; D002645:Chickens; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000502:physiology; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology* / Q000196:embryology / Q000502:physiology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics
D004792:Enzyme Precursors; D019717:Tissue Inhibitor of Metalloproteinase-3; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase