title: Response to Nodal morphogen gradient is determined by the kinetics of target gene induction.
abstract: Morphogen gradients expose cells to different signal concentrations and induce target genes with different ranges of expression. To determine how the Nodal morphogen gradient induces distinct gene expression patterns during zebrafish embryogenesis, we measured the activation dynamics of the signal transducer Smad2 and the expression kinetics of long- and short-range target genes. We found that threshold models based on ligand concentration are insufficient to predict the response of target genes. Instead, morphogen interpretation is shaped by the kinetics of target gene induction: the higher the rate of transcription and the earlier the onset of induction, the greater the spatial range of expression. Thus, the timing and magnitude of target gene expression can be used to modulate the range of expression and diversify the response to morphogen gradients.
authors: Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
authors: Julien
authors: J
authors: Dubrulle
authors: Department of Mathematics, College of Science and Engineering, University of Minnesota, Minneapolis, United States.
authors: Benjamin M
authors: BM
authors: Jordan
authors: Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
authors: Laila
authors: L
authors: Akhmetova
authors: Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
authors: Jeffrey A
authors: JA
authors: Farrell
authors: Division of Medicine, Medical University of South Carolina, Charleston, United States.
authors: Seok-Hyung
authors: SH
authors: Kim
authors: Department of Developmental Biology, Washington University School of Medicine, Saint Louis, United States.
authors: Lilianna
authors: L
authors: Solnica-Krezel
authors: Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
authors: Alexander F
authors: AF
authors: Schier
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000187:drug effects / Q000235:genetics; D004707:Endoderm / Q000187:drug effects / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D055457:Nodal Protein / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051899:Smad2 Protein / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D019076:Transgenes; D015027:Zebrafish / Q000196:embryology / Q000235:genetics
chemical_list: D055457:Nodal Protein; D051899:Smad2 Protein; D049452:Green Fluorescent Proteins
keywords: DNA binding affinity; developmental biology; morphogen gradient; signal transduction; stem cells; transcription rate; zebrafish