NF-kappa B mediates FGF signal regulation of msx-1 expression

The nuclear factor-kappaB (NF-kappaB) family of transcription factors is in volved in proliferation, differentiation, and apoptosis in a stage- and cel l-dependent manner. Recent evidence has shown that NF-kappaB activity is ne cessary for both chicken and mouse limb development. We report here that th e NF-kappaB family member c-rel and the homeodomain gene msx-1 have partial ly overlapping expression patterns in the developing chick limb. In additio n, inhibition of NF-kappaB activity resulted in a decrease in msx-1 mRNA ex pression. Sequence analysis of the msx-1 promoter revealed three potential kappaB-binding sites similar to the interferon-7 (IFN-gamma) kappaB-binding site. These sites bound to c-Rel, as shown by electrophoretic mobility shi ft assay (EMSA). Furthermore, inhibition of NF-kappaB activity significantl y reduced transactivation of the msx-1 promoter in response to FGF-2/-4, kn own stimulators of msx-1 expression. These results suggest that NF-kappaB m ediates the FGF-2/-4 signal regulation of msx-1 gene expression. (C) 2001 A cademic Press.