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

Yumi Kanegae, Ana Teresa Tavares, Juan Carlos Izpisúa Belmonte and Inder M. Verma ()
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Yumi Kanegae: The Salk Institute for Biological Studies
Ana Teresa Tavares: The Salk Institute for Biological Studies
Juan Carlos Izpisúa Belmonte: The Salk Institute for Biological Studies
Inder M. Verma: The Salk Institute for Biological Studies

Nature, 1998, vol. 392, issue 6676, 611-614

Abstract: Abstract The development of the vertebrate limb serves as an amenable system for studying signaling pathways that lead to tissue patterning and proliferation1. Limbs originate as a consequence of a differential growth of cells from the lateral plate mesoderm at specific axial levels2. 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 zone3,4,5,6. 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 transformation7. 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 transcription7. Here we show that Rel/NF-κB genes are expressed in the progress zone of the developing chick limb bud. When theactivity of Rel/NF-κB proteins is blocked by infection with viral 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.

Date: 1998
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DOI: 10.1038/33429

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