Feedback inhibition of Jak/STAT signaling by apontic is required to limit an invasive cell population.

TitleFeedback inhibition of Jak/STAT signaling by apontic is required to limit an invasive cell population.
Publication TypeJournal Article
Year of Publication2008
AuthorsStarz-Gaiano M, Melani M, Wang X, Meinhardt H, Montell DJ
JournalDev Cell
Date Published2008 May
KeywordsAlleles, Animals, CCAAT-Enhancer-Binding Proteins, Cell Movement, DNA-Binding Proteins, Drosophila melanogaster, Drosophila Proteins, Feedback, Physiological, Female, Gene Expression Regulation, Developmental, Janus Kinases, Ovarian Follicle, Protein Binding, Regulatory Sequences, Nucleic Acid, Signal Transduction, STAT Transcription Factors, Transcription Factors

<p>In both normal development and in a variety of pathological conditions, epithelial cells can acquire migratory and invasive properties. Border cells in the Drosophila ovary provide a genetically tractable model for elucidating the mechanisms controlling such behaviors. Here we report the identification of a mutant, apontic (apt), in which the migratory population expanded and separation from the epithelium was impeded. This phenotype resembled gain-of-function of JAK/STAT activity. Gain-of-function of APT also mimicked loss of function of STAT and its key downstream target, SLBO. APT expression was induced by STAT, which bound directly to sites in the apt gene. The data suggest that a regulatory circuit between STAT, APT, and SLBO functions to convert an initially graded signal into an all-or-nothing activation of JAK/STAT and thus to proper cell specification and migration. These findings are supported by a mathematical model, which accurately simulates wild-type and mutant phenotypes.</p>

Alternate JournalDev. Cell
PubMed ID18477455
Grant ListR01 AG063907 / AG / NIA NIH HHS / United States
R01 GM046425 / GM / NIGMS NIH HHS / United States
GM73164 / GM / NIGMS NIH HHS / United States
GM46425 / GM / NIGMS NIH HHS / United States