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- κB 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-κB is associated in the cytoplasm with an inhibitory protein, I-κB. In response to an external signal, I-κB is phosphorylated, ubiquitinated and degraded, releasing NF- κB to enter the nucleus and activate transcription. Here we show that Rel/NF-κB genes are expressed in the progress zone of the developing chick limb bud. When the activity of Rel/NF-κB proteins is blocked by infection with vital vectors that produce transdominant-negative I-κBα proteins, limb outgrowth is arrested. Our results indicate that Rel/NF-κB transcription factors play a role in vertebrate limb development.
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