A causative role of stromelysin-3 in extracellular matrix remodeling and epithelial apoptosis during intestinal metamorphosis in Xenopus laevis.
The matrix metalloproteinases are a family of proteases capable of degrading various components of the extracellular matrix. Expression studies have implicated the involvement of the matrix metalloproteinase stromelysin-3 (ST3) in tissue remodeling and pathogenesis. However, the in vivo role of ST3 has been difficult to study because of a lack of good animal models. Here we used intestinal remodeling during thyroid hormone-dependent metamorphosis of Xenopus laevis as a model to investigate in vivo the role of ST3 during postembryonic organ development in vertebrates. We generated transgenic tadpoles expressing ST3 under control of a heat shock-inducible promoter. We showed for the first time in vivo that wild type ST3 but not a catalytically inactive mutant was sufficient to induce larval epithelial cell death and fibroblast activation, events that normally occur only in the presence of thyroid hormone. We further demonstrated that these changes in cell fate are associated with altered gene expression in the intestine and remodeling of the intestinal basal lamina. These results thus suggest that ST3 regulates cell fate and tissue morphogenesis through direct or indirect ECM remodeling.
Fu
Liezhen
L
Laboratory of Gene Regulation and Development, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.
Ishizuya-Oka
Atsuko
A
Buchholz
Daniel R
DR
Amano
Tosikazu
T
Matsuda
Hiroki
H
Shi
Yun-Bo
YB
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D015152:Blotting, Northern; D002384:Catalysis; D016923:Cell Death; D019070:Cell Lineage; D018076:DNA, Complementary / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology; D004848:Epithelium / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006358:Hot Temperature; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000378:metabolism; D053507:Matrix Metalloproteinase 11; D008666:Metalloendopeptidases / Q000378:metabolism / Q000502:physiology*; D008675:Metamorphosis, Biological; D008854:Microscopy, Electron; D008957:Models, Genetic; D009154:Mutation; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013963:Thyroid Hormones / Q000378:metabolism; D013997:Time Factors; D019076:Transgenes; D014982:Xenopus laevis
D018076:DNA, Complementary; D013963:Thyroid Hormones; D049452:Green Fluorescent Proteins; D053507:Matrix Metalloproteinase 11; D008666:Metalloendopeptidases