Drs. Cantemir and Cai contributed equally to this work.
Tissue inhibitor of metalloproteinase-2 (TIMP-2) expression during cardiac neural crest cell migration and its role in proMMP-2 activation
Article first published online: 20 OCT 2004
Copyright © 2004 Wiley-Liss, Inc.
Volume 231, Issue 4, pages 709–719, December 2004
How to Cite
Cantemir, V., Cai, D.H., Reedy, M.V. and Brauer, P.R. (2004), Tissue inhibitor of metalloproteinase-2 (TIMP-2) expression during cardiac neural crest cell migration and its role in proMMP-2 activation. Dev. Dyn., 231: 709–719. doi: 10.1002/dvdy.20171
- Issue published online: 11 NOV 2004
- Article first published online: 20 OCT 2004
- Manuscript Accepted: 15 JUL 2004
- Manuscript Revised: 12 JUL 2004
- Manuscript Received: 27 JAN 2004
- American Heart Association-Heartland Affiliate. Grant Numbers: 00516382, 0355397Z
- neural crest;
- tissue inhibitors of metalloproteinases;
- cell migration;
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. Developmental Dynamics 231:709–719, 2004. © 2004 Wiley-Liss, Inc.