Role of Rel/NF-kappa B transcription factors during the outgrowth of the vertebrate limb

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The development of the vertebrate limb serves as an amenable system for studying signaling pathways that lead to tissue patterning and proliferation [1].Limbs originate as a consequence of a differential growth of cells from the lateral plate mesoderm at specific axial levels [2]. 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 [3-6]. The Rel/NF-kappa B family of transcription factors is induced in response to several signals that lead to cell growth, differentiation, inflammatory responses, apoptosis and neoplastic transformation [7]. In unstimulated cells, NF-kappa B is associated in the cytoplasm with an inhibitory protein, I-kappa B. In response to an external signal, I-kappa B is phosphorylated, ubiquitinated and degraded, releasing NF-kappa B to enter the nucleus and activate transcription [7]. Here we show that Rel/NF-kappa B genes are expressed in the progress zone of the developing chick limb bud. When the activity of Rel/NF-kappa B proteins is blocked by infection with viral vectors that produce transdominant-negative I-kappa B alpha proteins, limb outgrowth is arrested. Our results indicate that Rel/NF-kappa B transcription factors play a role in vertebrate limb development.

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