title: Role of Rel/NF-kappaB transcription factors during the outgrowth of the vertebrate limb.
abstract: 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-kappaB 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-kappaB is associated in the cytoplasm with an inhibitory protein, I-kappaB. In response to an external signal, I-kappaB is phosphorylated, ubiquitinated and degraded, releasing NF-kappaB to enter the nucleus and activate transcription. Here we show that Rel/NF-kappaB genes are expressed in the progress zone of the developing chick limb bud. When the activity of Rel/NF-kappaB proteins is blocked by infection with viral vectors that produce transdominant-negative I-kappaBalpha proteins, limb outgrowth is arrested. Our results indicate that Rel/NF-kappaB transcription factors play a role in vertebrate limb development.
authors.affiliation: The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Kanegae
authors.forename: A T
authors.initials: AT
authors.lastname: Tavares
authors.forename: J C
authors.initials: JC
authors.lastname: Izpisúa Belmonte
authors.forename: I M
authors.initials: IM
authors.lastname: Verma
mesh_terms: D000818:Animals; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000494:pharmacology; D047108:Embryonic Development; D004627:Embryonic Induction; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D018507:Gene Expression Regulation, Developmental; D005822:Genetic Vectors; D006133:Growth Substances / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D020672:I-kappa B Proteins; D018878:Limb Buds / Q000196:embryology*; D051957:MSX1 Transcription Factor; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D020569:Proto-Oncogene Proteins c-rel; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D051879:Twist-Related Protein 1
chemical_list: D004268:DNA-Binding Proteins; D006133:Growth Substances; D018398:Homeodomain Proteins; D020672:I-kappa B Proteins; D051957:MSX1 Transcription Factor; D016328:NF-kappa B; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D000072000:NF-KappaB Inhibitor alpha; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors