Interpretation of the UPD/JAK/STAT morphogen gradient in Drosophila follicle cells.
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.
Starz-Gaiano
Michelle
M
Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Melani
Mariana
M
Meinhardt
Hans
H
Montell
Denise
D
D000818:Animals; D002465:Cell Movement; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000502:physiology*; D053612:Janus Kinases / Q000378:metabolism*; D008954:Models, Biological; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
D029721:Drosophila Proteins; D050791:STAT Transcription Factors; D014157:Transcription Factors; D053612:Janus Kinases; C085845:hop protein, Drosophila