title: Prdm1 acts downstream of a sequential RA, Wnt and Fgf signaling cascade during zebrafish forelimb induction.
abstract: Vertebrate limb induction is triggered in the lateral plate mesoderm (LPM) by a cascade of signaling events originating in the axial mesoderm. While it is known that Fgf, Wnt and retinoic acid (RA) signals are involved in this cascade, their precise regulatory hierarchy has not been determined in any species. tbx5 is the earliest gene expressed in the limb bud mesenchyme. Recently, another transcription factor, Prdm1, has been shown to be crucial for zebrafish forelimb development. Here, we show that Prdm1 is downstream of RA, Wnt2b and Tbx5 activity. We find that RA activity, but not Fgf signaling, is necessary for wnt2b expression. Fgf signaling is required for prdm1 expression in the fin bud, but is not necessary for the initiation of tbx5 expression. We propose a model in which RA signaling from the somitic mesoderm leads to activation of wnt2b expression in the intermediate mesoderm, which then signals to the LPM to trigger tbx5 expression. tbx5 is required for Fgf signaling in the limb bud leading to activation of prdm1 expression, which in turn is required for downstream activation of fgf10 expression.
authors.affiliation: European Molecular Biology Laboratory (EMBL Heidelberg, Germany.
authors.forename: Nadia
authors.initials: N
authors.lastname: Mercader
authors.forename: Sabine
authors.initials: S
authors.lastname: Fischer
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Neumann
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins; D004625:Embryo, Nonmammalian / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005552:Forelimb / Q000196:embryology*; D006023:Glycoproteins / Q000502:physiology; D018878:Limb Buds / Q000502:physiology*; D008648:Mesoderm / Q000502:physiology*; D009024:Morphogenesis; D009154:Mutation; D009687:Nuclear Proteins; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology*; D014212:Tretinoin / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D006023:Glycoproteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C492033:wnt2ba protein, zebrafish; D014212:Tretinoin; D005346:Fibroblast Growth Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1; C513257:prdm1a protein, zebrafish