Bushdid P B, Brantley D M, Yull F E, Blaeuer G L, Hoffman L H, Niswander L, Kerr L D
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2363, USA.
Nature. 1998 Apr 9;392(6676):615-8. doi: 10.1038/33435.
In Drosophila, the Dorsal protein establishes the embryonic dorso-ventral axis during development. Here we show that the vertebrate homologue of Dorsal, nuclear factor-kappa B (NF-kappaB), is vital for the formation of the proximo-distal organizer of the developing limb bud, the apical ectodermal ridge (AER). Transcription of the NF-kappaB 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-kappaB 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-kappaB activity in limb mesenchyme leads to a reduction in expression of Sonic hedgehog and Twist but derepresses expression of the bone morphogenetic protein-4 gene. These results are the first evidence that vertebrate NF-kappaB proteins act to transmit growth factor signals between the ectoderm and the underlying mesenchyme during embryonic limb formation.
在果蝇中，背侧蛋白在发育过程中确立胚胎的背腹轴。在此我们表明，背侧蛋白在脊椎动物中的同源物——核因子κB（NF-κB），对于发育中的肢芽近端-远端组织者即顶端外胚层嵴（AER）的形成至关重要。NF-κB原癌基因c-rel的转录，在一定程度上，在肢芽形态发生过程中受AER衍生信号如成纤维细胞生长因子的调控。利用病毒介导的抑制剂递送阻断NF-κB活性会导致AER高度畸形、整体肢体尺寸减小、远端结构缺失以及肢体生长方向逆转。此外，抑制肢间充质中的NF-κB活性会导致音猬因子和Twist表达降低，但会解除骨形态发生蛋白-4基因的表达抑制。这些结果首次证明，在胚胎肢体形成过程中，脊椎动物NF-κB蛋白起到在外胚层和下方间充质之间传递生长因子信号的作用。
