Interpretation of the UPD/JAK/STAT morphogen gradient in Drosophila follicle cells

Cell Cycle. 2009 Sep 15;8(18):2917-25. doi: 10.4161/cc.8.18.9547. Epub 2009 Sep 16.

Abstract

We are using Drosophila follicle cells to study the mechanisms that promote cell motility. Using genetics we identified a gene regulatory network that controls the dynamic pattern of activation of JAK/STAT in anterior follicle cells. Under the influence of a graded signal, Unpaired (UPD), JAK/STAT becomes activated first in a graded fashion. STAT, in turn, locally activates its own repressor, Apontic (APT), a new feedback regulator of JAK/STAT signaling. High levels of JAK/STAT also activate Slow Border Cells (SLBO), which undermines APT-mediated repression. In this way, cells that achieve a high JAK/STAT level maintain SLBO expression and form border cells, which then migrate out of the cell layer. Cells with lower JAK/STAT activity express more APT than SLBO, ultimately lose STAT activity, and remain in the follicular epithelium. To better understand how the graded signal is converted to an all-or-none decision to move or stay, we developed a mathematical model. Simulations using the model reproduce the observed dynamics of JAK/STAT expression in the wild type and in several mutant situations. By combining biological experiments and mathematical modeling, we can achieve a more sophisticated understanding of how cells interpret molecular gradients.

MeSH terms

  • Animals
  • Cell Movement
  • Drosophila
  • Drosophila Proteins / metabolism*
  • Epithelial Cells / physiology*
  • Janus Kinases / metabolism*
  • Models, Biological*
  • STAT Transcription Factors / metabolism*
  • Signal Transduction
  • Transcription Factors / metabolism*

Substances

  • Drosophila Proteins
  • STAT Transcription Factors
  • Transcription Factors
  • Janus Kinases
  • hop protein, Drosophila