FGF-4 regulates expression of Evx-1 in the developing mouse limb.
We describe here the temporal and spatial pattern of expression of Evx-1, a murine homolog of the Drosophila even-skipped gene, in the developing limb bud. Evx-1 RNA is first detected in distal limb (progress zone) mesenchyme shortly after the formation of the apical ectodermal ridge. The level of Evx-1 RNA increases during the next 24 hours of development, and then decreases in the subsequent 24 hours, such that by the time the ridge regresses Evx-1 RNA is undetectable. At all these stages, Evx-1 RNA is localized primarily to the posterior distal mesenchyme, in the region immediately underlying that portion of the ridge in which the Fgf-4 gene is expressed. Using an in vitro culture system, we show that the ridge is required for both the induction and maintenance of Evx-1 expression in the distal mesenchyme. We also demonstrate that in the absence of the ridge, FGF-4, as well as other FGF proteins, can induce Evx-1 expression in the limb bud. However, this effect appears to be indirect, since it can be blocked by an inhibitor of protein synthesis. Additional studies demonstrate that the effect of FGF-4 on Evx-1 expression is modulated by BMP-2. These data serve to identify Evx-1 as a downstream gene in the FGF signal transduction pathway in the limb.
Niswander
L
L
Department of Anatomy, School of Medicine, University of California, San Francisco 94143-0452.
Martin
G R
GR
D000818:Animals; D019485:Bone Morphogenetic Proteins; D046508:Culture Techniques; D004475:Ectoderm / Q000502:physiology; D004627:Embryonic Induction / Q000502:physiology*; D005121:Extremities / Q000196:embryology*; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D005801:Genes, Homeobox / Q000235:genetics*; D005855:Germ Layers / Q000502:physiology*; D006133:Growth Substances / Q000235:genetics; D017403:In Situ Hybridization; D008648:Mesoderm / Q000502:physiology; D051379:Mice; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D012313:RNA / Q000032:analysis
D019485:Bone Morphogenetic Proteins; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D006133:Growth Substances; D011506:Proteins; D011518:Proto-Oncogene Proteins; D005346:Fibroblast Growth Factors; D012313:RNA