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

TitleInterpretation of the UPD/JAK/STAT morphogen gradient in Drosophila follicle cells.
Publication TypeJournal Article
Year of Publication2009
AuthorsStarz-Gaiano M, Melani M, Meinhardt H, Montell D
JournalCell Cycle
Volume8
Issue18
Pagination2917-25
Date Published2009 Sep 15
ISSN1551-4005
KeywordsAnimals, Cell Movement, Drosophila, Drosophila Proteins, Epithelial Cells, Janus Kinases, Models, Biological, Signal Transduction, STAT Transcription Factors, Transcription Factors
Abstract

<p>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.</p>

DOI10.4161/cc.8.18.9547
Alternate JournalCell Cycle
PubMed ID19729999
PubMed Central IDPMC3021920
Grant ListR01 GM046425 / GM / NIGMS NIH HHS / United States
R01 GM046425-18A1 / GM / NIGMS NIH HHS / United States