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

Nature volume 392, pages 611–614 (1998)Cite this article

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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.

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Figure 1: Expression of Rel/NF-κB and other proteins involved in chick limb development.
Figure 2: Characterization of transdominant-negative mutants of mouse I-κBα.
Figure 3: Blocking Rel/NF-κB signalling inhibits limb outgrowth.
Figure 4: Blocking Rel/NF-κB signalling alters gene expression in the developing limb.

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Change history

  • 16 June 2014

    Owing to an HTML symbol conversion error the superscript number 2 for author A.T.T. should have been 3; the error was corrected on 16 June 2014.

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Acknowledgements

We thank T. Gilmore, R. Hrdlickova and H. R. Bose for reagents; M. Pando, D. Van Antwerp, I Saito, C. Rays, J. De La Peña, C. De La Peña and C. Rodriguez-Esteban for suggestions and help with virus infection and in situ hybridizations; and B. Coyne and L. Hooks for help in assembling the manuscript. Y.K. is on leave of absence from the Institute of Medical Science, The University of Tokyo. This work was supported by a fellowship from the Gulbenkian Foundation (PGDBM) and Program PRAXIS XXI (A.T.T.), grants from the NIH, NIH and the Wayne and Gladys Valley Foundation (I.M.V.) and grants from the NSF, NIH and the G. Harold and Leyla Y. Mathers Charitable Foundation (J.C.I.B.). J.C.I.B. is a Pew Scholar. I.M.V. is an American Cancer Society Professor of Molecular Biology.

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Author notes

  1. Yumi Kanegae

    Present address: Institute of Molecular Genetics, University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo, 108-8639, Japan

  2. Yumi Kanegae and Ana Teresa Tavares: These authors contributed equally to this work.

Authors and Affiliations

  1. The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, 92037, California, USA

    Yumi Kanegae, Ana Teresa Tavares, Juan Carlos Izpisúa Belmonte & Inder M. Verma

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  1. Yumi Kanegae
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  2. Ana Teresa Tavares
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  3. Juan Carlos Izpisúa Belmonte
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  4. Inder M. Verma
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Correspondence to Inder M. Verma.

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Kanegae, Y., Tavares, A., Belmonte, J. et al. Role of Rel/NF-κB transcription factors during the outgrowth of the vertebrate limb. Nature 392, 611–614 (1998). https://doi.org/10.1038/33429

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