Response to Nodal morphogen gradient is determined by the kinetics of target gene induction
Julien Dubrulle,
Benjamin M Jordan,
Laila Akhmetova,
Jeffrey A Farrell,
Seok-Hyung Kim,
Lilianna Solnica-Krezel,
Alexander F Schier
Affiliations
Julien Dubrulle
Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
Benjamin M Jordan
Department of Mathematics, College of Science and Engineering, University of Minnesota, Minneapolis, United States; Department of Organismal and Evolutionary Biology, Harvard University, Cambridge, United States
Laila Akhmetova
Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
Jeffrey A Farrell
Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
Seok-Hyung Kim
Division of Medicine, Medical University of South Carolina, Charleston, United States
Lilianna Solnica-Krezel
Department of Developmental Biology, Washington University School of Medicine, Saint Louis, United States; Department of Medicine, Vanderbilt University Medical Center, Nashville, United States
Alexander F Schier
Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States; Harvard Stem Cell Institute, Harvard University, Cambridge, United States; Broad Institute of MIT and Harvard, Cambridge, United States; Center for Brain Science, Harvard University, Cambridge, United States; Center for Systems Biology, Harvard University, Cambridge, United States
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.
