ROLE OF REL NF-KAPPA-B TRANSCRIPTION FACTORS DURING THE OUTGROWTH OF THE VERTEBRATE LIMB/

The development of the vertebrate limb serves as an amenable system fo r studying signaling pathways that lead to tissue patterning and proli feration(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 g roup of mesenchymal cells, induces the overlying ectoderm to different iate into a specialized structure termed the apical ectodermal ridge. Subsequent limb outgrowth requires reciprocal signalling between the r idge and the progress zone(3-6). The Rel/NF-kappa B family of transcri ption factors is induced in response to several signals that lead to c ell growth, differentiation, inflammatory responses, apoptosis and neo plastic transformation(7), In unstimulated cells, NF-kappa B is associ ated in the cytoplasm with an inhibitory protein, I-kappa B. In respon se to an external signal, I-kappa B is phosphorylated, ubiquitinated a nd degraded, releasing NF-kappa B to enter the nucleus and activate tr anscription(7). Here we show that Rel/NF-kappa B genes are expressed i n the progress zone of the developing chick limb bud. When the activit y of Rel/NF-kappa B proteins is blocked by infection with viral vector s that produce transdominant-negative I-kappa B alpha proteins, limb o utgrowth is arrested, Our results indicate that Rel/NF-kappa B transcr iption factors play a role in vertebrate limb development.