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Matrix metalloproteinases (MMPs) play important roles in the turnover of components of extracellular matrix (ECM) and in the processing of active and latent-signaling molecules bound to the ECM or associated with the cell surface. Through such actions, MMPs regulate a variety of cellular and developmental processes. Membrane-type matrix metalloproteinases (MT-MMPs) are of particular importance because they function in the immediate pericellular environment that modulates both cell-cell and cell-ECM interactions. In this study, we utilized zebrafish as a developmental model to study the role of MT-MMPs during early embryogenesis. We successfully isolated two isoforms of a MT-MMP homologue that are structurally similar to MT1-MMP. They have been named zebrafish MT-MMPalpha and beta. Zebrafish MT-MMPbeta is unique among vertebrate MT-MMPs in that it contains an Arg-Glu-Asp (RED) multiple-repeat motif in its linker region. Whole mount in situ analysis, RT-PCR, immunofluorescence, reporter analysis, Western blot analysis, and zymography indicated that MT-MMPalpha and beta were expressed through at least the first 72 h of development and that this expression was targeted to the cell surface. Functional studies using injection of either mRNA or morpholino antisense oligonucleotides resulted in a truncation of the cranial to caudal axis as monitored through 72 h post fertilization, indicating that zebrafish MT-MMPalpha and beta had an important role in embryonic development. Axis markers indicated that these effects likely involved processes occurring later than 10 h of embryogenesis.

Original publication

DOI

10.1016/s0945-053x(03)00020-9

Type

Journal article

Journal

Matrix biology : journal of the International Society for Matrix Biology

Publication Date

05/2003

Volume

22

Pages

279 - 293

Addresses

Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.

Keywords

Cell Membrane, Animals, Zebrafish, Humans, Metalloendopeptidases, Isoenzymes, DNA, Complementary, In Situ Hybridization, Species Specificity, Gene Expression Regulation, Developmental, Gene Expression Regulation, Enzymologic, Amino Acid Sequence, Base Sequence, Sequence Homology, Amino Acid, Genes, Reporter, Molecular Sequence Data, Matrix Metalloproteinases, Membrane-Associated