1: Dev Biol. 2001 Sep 1;237(1):107-15. 

NF-kappaB mediates FGF signal regulation of msx-1 expression.

Bushdid PB, Chen CL, Brantley DM, Yull F, Raghow R, Kerr LD, Barnett JV.

Department of Microbiology and Immunology, Vanderbilt University, Nashville,
Tennessee 37232, USA. buslb9@chmcc.org

The nuclear factor-kappaB (NF-kappaB) family of transcription factors is
involved in proliferation, differentiation, and apoptosis in a stage- and
cell-dependent manner. Recent evidence has shown that NF-kappaB activity is
necessary for both chicken and mouse limb development. We report here that the
NF-kappaB family member c-rel and the homeodomain gene msx-1 have partially
overlapping expression patterns in the developing chick limb. In addition,
inhibition of NF-kappaB activity resulted in a decrease in msx-1 mRNA
expression. Sequence analysis of the msx-1 promoter revealed three potential
kappaB-binding sites similar to the interferon-gamma (IFN-gamma) kappaB-binding
site. These sites bound to c-Rel, as shown by electrophoretic mobility shift
assay (EMSA). Furthermore, inhibition of NF-kappaB activity significantly
reduced transactivation of the msx-1 promoter in response to FGF-2/-4, known
stimulators of msx-1 expression. These results suggest that NF-kappaB mediates
the FGF-2/-4 signal regulation of msx-1 gene expression. Copyright 2001 Academic
Press.

PMID: 11518509 [PubMed - indexed for MEDLINE]


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2: Nature. 1998 Apr 9;392(6676):611-4. 

Comment in:
    Nature. 1998 Apr 9;392(6676):547-9.
    Nature. 1998 Sep 17;395(6699):230-1.

Role of Rel/NF-kappaB transcription factors during the outgrowth of the
vertebrate limb.

Kanegae Y, Tavares AT, Izpisua Belmonte JC, Verma IM.

The Salk Institute for Biological Studies, La Jolla, California 92037, USA.

The development of the vertebrate limb serves as an amenable system for studying
signaling pathways that lead to tissue patterning and proliferation. Limbs
originate as a consequence of a differential growth of cells from the lateral
plate mesoderm at specific axial levels. At the tip of the limb primordia the
progress zone, a proliferating group of mesenchymal cells, induces the overlying
ectoderm to differentiate into a specialized structure termed the apical
ectodermal ridge. Subsequent limb outgrowth requires reciprocal signalling
between the ridge and the progress zone. The Rel/NF-kappaB family of
transcription factors is induced in response to several signals that lead to
cell growth, differentiation, inflammatory responses, apoptosis and neoplastic
transformation. In unstimulated cells, NF-kappaB is associated in the cytoplasm
with an inhibitory protein, I-kappaB. In response to an external signal,
I-kappaB is phosphorylated, ubiquitinated and degraded, releasing NF-kappaB to
enter the nucleus and activate transcription. Here we show that Rel/NF-kappaB
genes are expressed in the progress zone of the developing chick limb bud. When
the activity of Rel/NF-kappaB proteins is blocked by infection with viral
vectors that produce transdominant-negative I-kappaBalpha proteins, limb
outgrowth is arrested. Our results indicate that Rel/NF-kappaB transcription
factors play a role in vertebrate limb development.

PMID: 9560158 [PubMed - indexed for MEDLINE]


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