Inhibition of NF(-κ)B activity results in disruption of the apical ectodermal ridge and aberrant limb morphogenesis Journal Article
| Authors: | Bushdid, P. B.; Brantley, D. M.; Yull, F. E.; Blaeuer, G. L.; Hoffman, L. H.; Niswander, L.; Kerr, L. D. |
| Article Title: | Inhibition of NF(-κ)B activity results in disruption of the apical ectodermal ridge and aberrant limb morphogenesis |
| Abstract: | In Drosophila, the Dorsal protein establishes the embryonic dorso- ventral axis during development. Here we show that the vertebrate homo1ogue of Dorsal, nuclear factor-kappa B (NF-κB), is vital for the formation of the proximo-distal organizer of the developing limb bud, the apical ectodermal ridge (AER). Transcription of the HF-κB proto-oncogene c-rel is regulated, in part, during morphogenesis of the limb bud by AER-derived signals such as fibroblast growth factors. Interruption of NF-κB activity using viral- mediated delivery of an inhibitor results in a highly dysmorphic AER, reduction in overall limb size, loss of distal elements and reversal in the direction of limb outgrowth. Furthermore, inhibition of NF-κB activity in limb mesenchyme leads to a reduction in expression of Sonic hedgehog and T~ but derepresses expression of the bone morphogenetic protein-4 gene. These results are the first evidence that vertebrate NF-κB proteins act to transmit growth factor signals between the ectoderm and the underlying mesenchyme during embryonic limb formation. |
| Keywords: | signal transduction; dna binding protein; oncoprotein; genetics; dna-binding proteins; proto-oncogene proteins; nonhuman; animal; animals; proto oncogene; embryo; sonic hedgehog protein; animal experiment; hedgehog proteins; drosophila; embryo development; morphogenesis; immunoglobulin enhancer binding protein; physiology; gene vector; genetic vectors; gene expression regulation; prenatal development; gene expression regulation, developmental; biosynthesis; drug antagonism; protein synthesis; transactivator protein; nf-kappa b; protein biosynthesis; trans-activators; culture technique; tissue differentiation; retrovirus; retroviridae; adenoviridae; chick embryo; adenovirus; ectoderm; limb development; i kappa b; transcription factor rel; embryo induction; embryonic induction; limb bud; proto-oncogene proteins c-rel; i-kappa b proteins; priority journal; article; culture techniques; nf kappab inhibitor alpha; nf-kappab inhibitor alpha |
| Journal Title: | Nature |
| Volume: | 392 |
| Issue: | 6676 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1998-04-09 |
| Start Page: | 615 |
| End Page: | 618 |
| Language: | English |
| DOI: | 10.1038/33435 |
| PUBMED: | 9560159 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
