Signaling specificities of fibroblast growth factor receptors in early Xenopus embryo.
Formation of mesoderm and posterior structures in early Xenopus embryos is dependent on fibroblast growth factor (FGF) signaling. Although several FGF receptors (FGFRs) are expressed in the early embryo, their respective role in these processes remains poorly understood. We provide evidence that FGFR-1 and FGFR-4 signals elicit distinct responses both in naive and neuralized ectodermal cells. We show that naive ectodermal cells expressing a constitutively active chimeric torso-FGFR-1 (t-R1) are converted into mesoderm in a Ras-dependent manner, while those expressing torso-FGFR-4 (t-R4) differentiate into epidermis without significant activation of Erk-1. In neuralized ectoderm, expression of t-R4 causes the up-regulation of the midbrain markers En-2 and Wnt-1, but not of the hindbrain nor the spinal cord markers Krox20 and Hoxb9. Mutation of tyr(776) in the phospholipase C-(gamma) binding consensus sequence YLDL of t-R4 completely abolishes En-2 and Wnt-1 induction. In contrast to t-R4, platelet derived growth factor (PDGF)-dependent FGFR-1 activation in neuralized ectodermal cells expressing a chimeric PDGFR-FGFR-1 receptor results in the expression of Krox20 and Hoxb9. A similar effect is observed when an inducible form of oncogenic Raf is expressed, therefore implicating FGFR-1 and Raf in the transduction of FGF-caudalizing signals in neural tissue. Our results suggest that FGFR-1 and FGFR-4 transduce distinct signals in embryonic cells, and mainly differ in their ability to activate the Ras/MAPK pathway.
Umbhauer
M
M
Laboratoire de Biologie Moléculaire et Cellulaire du Développement, groupe Biologie Expérimentale, UMR CNRS 7622, Université Paris VI, 75005 Paris, France.
Penzo-Méndez
A
A
Clavilier
L
L
Boucaut
J
J
Riou
J
J
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051767:Early Growth Response Protein 2; D004475:Ectoderm / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008648:Mesoderm / Q000502:physiology; D016296:Mutagenesis / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009420:Nervous System / Q000196:embryology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051499:Receptor, Fibroblast Growth Factor, Type 4; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029867:Xenopus Proteins; D014982:Xenopus laevis; D029961:Zebrafish Proteins; D000099266:Engrailed 2 Protein
D004268:DNA-Binding Proteins; D051767:Early Growth Response Protein 2; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D019908:Proto-Oncogene Proteins c-raf; D012333:RNA, Messenger; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051499:Receptor, Fibroblast Growth Factor, Type 4; D017468:Receptors, Fibroblast Growth Factor; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D000099266:Engrailed 2 Protein; C497329:EGR2 protein, Xenopus; C491256:Hoxb9 protein, Xenopus; C495249:WNT1 protein, Xenopus; C496357:Fgfr2 protein, Xenopus