PUBLICATION

The expression of novel membrane-type matrix metalloproteinase isoforms is required for normal development of zebrafish embryos

Authors
Zhang, J., Bai, S., Zhang, X., Nagase, H., and Sarras, M.P.
ID
ZDB-PUB-030716-5
Date
2003
Source
Matrix biology : journal of the International Society for Matrix Biology   22(3): 279-293 (Journal)
Registered Authors
Sarras, Michael P., Jr.
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Membrane/enzymology
  • DNA, Complementary/genetics
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Enzymologic
  • Genes, Reporter
  • Humans
  • In Situ Hybridization
  • Isoenzymes/genetics
  • Isoenzymes/metabolism
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases/genetics
  • Metalloendopeptidases/metabolism*
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
PubMed
12853038 Full text @ Matrix Biol.
Abstract
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping