Cloning and developmental characterization of Xenopus laevis membrane type-3 matrix metalloproteinase (MT3-MMP).
Proper extracellular matrix (ECM) remodeling, mediated by matrix metalloproteinases (MMPs), is crucial for the development and survival of multicellular organisms. Full-length Xenopus laevis membrane type-3 matrix metallo proteinase (MT3-MMP) was amplified by PCR and cloned from a stage 28 Xenopus head cDNA library. A comparison of the derived Xenopus MT3-MMP protein sequence to that of other vertebrates revealed 86% identity with human and mouse and 85% identity with chicken. The expression profile of MT3-MMP was examined during Xenopus embryogenesis: MT3-MMP transcripts were first detected at the later stages of development and were localized to dorsal and anterior structures. During metamorphosis and in the adult frog, MT3-MMP expression was restricted to specific tissues and organs. Treatment of Xenopus embryos with lithium chloride (LiCl), ultraviolet irradiation (UV), or retinoic acid (RA) revealed that MT3-MMP levels increased with LiCl-dorsalizing treatments and decreased with UV-ventralizing and RA-anterior neural truncating treatments. Overexpression of MT3-MMP through RNA injections led to dose-dependent developmental abnormalities and death. Moreover, MT3-MMP overexpression resulted in neural and head structure abnormalities, as well as truncated axes. Taken together, these results indicate that MT3-MMP expression in Xenopus is spatially and temporally restricted. Furthermore, deregulation of MT3-MMP during early embryogenesis has detrimental effects on development.
Hammoud
Lamis
L
Department of Physiology and Pharmacology, University of Western Ontario, London, Canada.
Walsh
Logan A
LA
Damjanovski
Sashko
S
D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000528:radiation effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D018021:Lithium Chloride / Q000494:pharmacology; D053513:Matrix Metalloproteinase 16; D020782:Matrix Metalloproteinases / Q000235:genetics*; D053504:Matrix Metalloproteinases, Membrane-Associated; D000090023:Metallothionein 3; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014212:Tretinoin / Q000494:pharmacology; D014466:Ultraviolet Rays; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*
D018076:DNA, Complementary; C507102:MMP16 protein, human; D000090023:Metallothionein 3; C507104:Mmp16 protein, mouse; C000715430:Mt3 protein, mouse; D012333:RNA, Messenger; D014212:Tretinoin; D053513:Matrix Metalloproteinase 16; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D018021:Lithium Chloride