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XB-ART-35104
PLoS One 2006 Dec 27;1:e106. doi: 10.1371/journal.pone.0000106.
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An NF-kappaB and slug regulatory loop active in early vertebrate mesoderm.

Zhang C , Carl TF , Trudeau ED , Simmet T , Klymkowsky MW .


Abstract
BACKGROUND: In both Drosophila and the mouse, the zinc finger transcription factor Snail is required for mesoderm formation; its vertebrate paralog Slug (Snai2) appears to be required for neural crest formation in the chick and the clawed frog Xenopus laevis. Both Slug and Snail act to induce epithelial to mesenchymal transition (EMT) and to suppress apoptosis. METHODOLOGY & PRINCIPLE FINDINGS: Morpholino-based loss of function studies indicate that Slug is required for the normal expression of both mesodermal and neural crest markers in X. laevis. Both phenotypes are rescued by injection of RNA encoding the anti-apoptotic protein Bcl-xL; Bcl-xL's effects are dependent upon IkappaB kinase-mediated activation of the bipartite transcription factor NF-kappaB. NF-kappaB, in turn, directly up-regulates levels of Slug and Snail RNAs. Slug indirectly up-regulates levels of RNAs encoding the NF-kappaB subunit proteins RelA, Rel2, and Rel3, and directly down-regulates levels of the pro-apopotic Caspase-9 RNA. CONCLUSIONS/SIGNIFICANCE: These studies reveal a Slug/Snail-NF-kappaB regulatory circuit, analogous to that present in the early Drosophila embryo, active during mesodermal formation in Xenopus. This is a regulatory interaction of significance both in development and in the course of inflammatory and metastatic disease.

PubMed ID: 17205110
PMC ID: PMC1762408
Article link: PLoS One
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: bcl2l1 casp9 menf.1 nfkb1 nfkb2 odc1 ptk2b rel rela relb snai1 snai2 sox3 sox9 tbxt vegt
Morpholinos: snai2 MO1


Article Images: [+] show captions
References [+] :
Ashraf, The mesoderm determinant snail collaborates with related zinc-finger proteins to control Drosophila neurogenesis. 1999, Pubmed